Engineering surface epitopes to improve protein crystallization

ABSTRACT

The invention provides for methods and systems for engineering target proteins, based on protein sequence characteristics that influence the likelihood of obtaining a crystal suitable for X-ray structure solution, to improve protein crystallization, as well as related material.

This application is a continuation of U.S. patent application Ser. No. 14/437,467, filed Apr. 21, 2015, which claims the benefit of and priority to International Application No. PCT/US2013/065748, filed Oct. 18, 2013, which claims the benefit of U.S. provisional patent application Ser. No. 61/956,167 filed Oct. 20, 2012, the disclosure of all of which is hereby incorporated by reference in its entirety for all purposes. This patent disclosure contains material that is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure as it appears in the U.S. Patent and Trademark Office patent file or records, but otherwise reserves any and all copyright rights.

All patents, patent applications and publications cited herein are hereby incorporated by reference in their entirety. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described herein.

GOVERNMENT INTERESTS

This invention was made with government support under grants GM074958, GM072867, GM062413, and GM075026 awarded by the National Institutes of Health. The Government has certain rights in this invention.

INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ELECTRONICALLY

This application contains a sequence listing. It has been submitted electronically via EFS-Web as an ASCII text file entitled “SeqListing0019240-00773WO2_SL_EN.txt” The sequence listing is 1,356 KB in size, and was created on Oct. 18, 2013. It is hereby incorporated by reference in its entirety.

BACKGROUND OF THE INVENTION

Current understanding of biology makes great use of atomic level protein structures, but the generation of these structures, e.g., by X-ray crystallography, is both expensive and uncertain. A significant bottleneck in the process is the generation of high quality crystals for X-ray diffraction. Much effort has gone to developing crystallization screens, and to creating high-throughput methods for cloning and expressing proteins (see, e.g., Acton T. B. et al., Methods Enzymol. 2005, 394, 210-243). However, the mechanisms of crystallization—and the protein characteristics that impact it—remain largely unknown and poorly understood, with different methods of study yielding substantially different results.

The Surface Entropy Reduction (SER) methods, identify mutations that can potentially improve crystallization by using secondary structure prediction and sequence conservation to locate residues with high-entropy side chains in variable loop regions of the protein. Replacing one or more of these residues with a low-entropy amino acid, like alanine, has been predicted to improve crystallization by reducing the entropic penalty of inter-protein interface formation. Moreover, this approach focuses on making mutations in predicted loop regions of the protein's secondary structure.

The methods described herein differ from the SER methods by using the Protein Data Bank (PDB) as a data mine of information to improve predictions. By using a topological analysis of crystal structures in the PDB, this is a novel approach to identifying possible mutations to improve crystallization. The methods described herein are superior as information is culled for improving interface formation from interfaces already experimentally observed. Moreover, unlike the SER methods, the methods and systems described herein use whole epitope modifications, rather than single amino acid changes, thus increasing the success rate at which an inter-protein interface could be formed, since interfaces are usually comprised of a surface and not a single residue interaction.

The epitope modifications involve chemical changes of very diverse types, including hydrophobic-to-hydrophilic substitutions in equal measure to hydrophilic-to-hydrophobic mutations, whereas the single-residue mutations suggested by SER involves primarily hydrophilic-to-hydrophobic substitutions and almost always polarity-reducing mutations. Such mutations tend to impair solubility, which prevents effective protein purification and crystallization. The greater diversity in the kinds of chemical changes involved in epitope modification fundamentally frees crystallization engineering from the crippling correlation between crystallization-improving and solubility-impairing mutations. Epitope modifications frequently involve increasing the side-chain entropy, so they do not require entropy reduction at the level of individual amino acids, which is the foundation of the SER method.

Finally, SER methods avoid mutations for non-loop regions of the protein, missing out on many potential epitopes in α-helices, helix capping motifs, or beta hairpins. The epitope engineering method described herein includes all secondary structure elements, thus generating a larger computational list of possible epitope candidates.

SUMMARY OF THE INVENTION

The invention is based, in part, on the finding that replacement of certain epitopes in a protein with more desirable epitopes, some of which occur in non-loop regions of the protein, significantly improves crystallization properties of the protein for purposes of X-ray crystallographic studies.

It is understood that any of the embodiments described below can be combined in any desired way, and any embodiment or combination of embodiments can be applied to each of the aspects described below.

In one embodiment, the invention provides for a method of modifying a protein sequence for high-resolution X-ray crystallographic structure determination, the method comprising: (a) receiving a sequence of a protein of interest; (b) selecting, using a computer, an epitope from an epitope library that is expected to increase the propensity of the protein of interest to crystallize and that is consistent with sequence variations observed in homologous proteins; and (c) outputting information on which portion of the amino acid sequence of the protein of interest should be replaced with the selected epitope to generate a modified protein.

In another embodiment of the invention, the information is outputted in the form of an amino acid sequence of the modified protein or a portion thereof. In another embodiment of the invention, the information is outputted in the form of a list of mutations to be made in the amino acid sequence of the protein of interest to provide the amino acid sequence of the modified protein or a portion thereof. In some embodiments, the information is outputted in the order that is a function of its likelihood of improving crystallization of the target protein.

In some embodiments, the epitope library includes information describing over-representation of an epitope in the PDB database.

In another embodiment of the invention, the method further comprises predicting the secondary structure of the protein of interest and of its homolog. In another embodiment, the method further comprises identifying a homolog of the protein of interest and aligning the sequence of the protein of interest with the sequence of the homolog.

In one embodiment, the epitope is selected based on one or more of: over-representation P-value for overrepresentation of the epitope in the epitope library; fraction of occurrences of the epitope in the PDB database in crystal-packing contacts; frequency of occurrence of the epitope in crystal-packing interfaces in the PDB database; sequence diversity of proteins containing the epitope in crystal-packing interfaces in the PDB database; sequence diversity of partner epitopes in the PDB database; low frequency of non-water bridging ligands to the epitope in the PDB database; lack of increase in hydrophobicity of the modified protein by introducing the epitope; or predicted influence of the epitope on the solubility of the modified protein.

In another embodiment, the selected epitope is 1-6 amino acid in length. In yet another embodiment, the selected epitope is 2-15 amino acids in length. In still another embodiment, the selected epitope is 4-15 amino acids in length. In another embodiment, the selected epitope is 4-6 amino acids in length.

In a further embodiment, the epitope includes a polar amino acid. In another embodiment of the invention, the selected epitope is an epitope from Tables 5-38. In another embodiment, the selected epitope is an epitope from Tables 2-3. In yet another embodiment, the selected epitope is an epitope from other tables generated using equivalent computational approaches to those described herein with obvious modification consistent with the concepts and principles described herein.

In another embodiment, the invention provides for the method where two or more steps are performed using a computer. In another embodiment, the method is implemented by a web-based server.

In a further embodiment, the invention provides for generating a nucleic acid sequence encoding a protein comprising the modified protein. The invention also provides for a method further comprising expressing the modified protein in a cell or in an in vitro expression system. In another embodiment, the method further comprises crystallizing the modified protein of interest.

In one aspect, the invention provides for a system for designing a modified protein for high-resolution X-ray crystallographic structure determination, the system comprising a computer having a processor and computer-readable program code for performing the method of modifying a protein sequence for high-resolution X-ray crystallographic structure determination, the method comprising: (a) receiving a sequence of a protein of interest; (b) selecting, using a computer, an epitope from an epitope library that is expected to increase the propensity of the protein of interest to crystallize and that is consistent with sequence variations observed in homologous proteins; and (c) outputting information on which portion of the amino acid sequence of the protein of interest should be replaced with the selected epitope to generate a modified protein.

The invention also provides for a method of using the system to obtain the amino acid sequence of the modified protein. The invention also provides for a method or a system further comprising generating a nucleic acid sequence encoding a protein comprising the modified protein. The invention also provides a method further comprising expressing the modified protein in a cell or in an in vitro expression system. In another embodiment, the invention provides for a method further comprising crystallizing the modified protein.

In another aspect, the invention provides for a computer readable medium containing a database of a plurality of epitopes from Tables 2-3 and 5-38 or other tables generated using equivalent computational approaches to those described herein. In some embodiments, the computer readable medium contains a database of at least 100 epitopes from Tables 2-3 and 5-38. In yet another aspect, the invention provides for a computer readable medium containing information describing over-representation of a plurality of epitopes in the PDB database. In some embodiments, the computer readable medium is non-transitory.

In yet another aspect, the invention provides for a recombinant protein in which a portion of its amino acid sequence has been replaced by an epitope from Tables 2-3 and 5-36 or from other tables generated using equivalent computational approaches to those described herein. In still another aspect, the invention provides for a crystal of the protein of interest which is obtained using the methods of the invention. In one embodiment, the crystal is suitable for high-resolution X-ray crystallographic studies.

In one embodiment, the expression system is an in vitro expression system. In another embodiment, the in vitro expression system is a cell-free transcription/translation system. In still another embodiment, the expression system is an in vivo expression system. In yet another embodiment, the in vivo expression system is a bacterial expression system or a eukaryotic expression system. In another embodiment, the in vivo expression system is an Escherichia coli cell. In still another embodiment, the in vivo expression system is a mammalian cell.

In one embodiment, the protein of interest is a human polypeptide, or a fragment thereof. In another embodiment, the protein of interest is a viral polypeptide, or a fragment thereof. In another embodiment, the protein of interest is an antibody, an antibody fragment, an antibody derivative, a diabody, a tribody, a tetrabody, an antibody dimer, an antibody trimer or a minibody. In another embodiment, the protein of interest is a target of pharmaceutical compound or a receptor. In still another embodiment, the antibody fragment is a Fab fragment, a Fab′ fragment, a F(ab)2 fragment, a Fd fragment, a Fv fragment, or a ScFv fragment. In yet another embodiment, the protein of interest is a cytokine, an inflammatory molecule, a growth factor, a cytokine receptor, an inflammatory molecule receptor, a growth factor receptor, an oncogene product, or any fragment thereof. In another yet another embodiment, the protein of interest is a fusion polypeptide. In one aspect, the invention described herein relates to a protein of interest produced by the methods described herein. In one aspect, the invention described herein relates to a pharmaceutical composition comprising the protein of interest produced by the methods described herein. In one aspect, the invention described herein relates to an immunogenic composition comprising the protein of interest produced by the methods described herein.

In one aspect, the invention provides for the use of packing epitopes from previously determined X-ray crystal structures in engineering of proteins with improved crystallization properties.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a diagram of epitope library generation according to one embodiment of the invention.

FIGS. 2A-2I show characteristics of oligomeric vs. crystal packing interfaces. Distributions are shown for three levels of interaction classification: half-interfaces (FIG. 2A, FIG. 2B, and FIG. 2C), full binary interaction epitopes (FIG. 2D, FIG. 2E, and FIG. 2F), and elementary binary interaction epitopes (FIG. 2G, FIG. 2H, and FIG. 2I). Distributions show the number of counts of the relevant element binned by buried surface area (FIG. 2A, FIG. 2D, and FIG. 2G), number of participating residues (FIG. 2B, FIG. 2E, and FIG. 2H), and spread—the number of residues, interacting or not, spanned by the element (FIG. 2C, FIG. 2F, and FIG. 2I). Within each graph, separate distributions are shown for all elements, elements which appear in the BioMT database of inferred biological oligomers, elements which do not appear in BioMT but are within proper interfaces, and elements which do not appear in BioMT and are not proper interfaces. All counts are redundancy-culled.

FIG. 3 is a graphical representation of the analytical scheme for crystal-packing analysis. Definitions of elements in the packing interface are given next to schematic depictions of each element. Bold lines represent protein chains, grey lines inter-atomic contacts ≤4 Å, and numbered circles show representative elements.

FIGS. 4A-4C show polymorphism in crystal packing interactions. FIG. 4A: Color-ramped 2-dimensional histogram for 3,185,367 pairs of interfaces from crystal structures of proteins with ≥98% sequence identity showing the percentage of pairwise residue interactions conserved versus the PSS (packing similarity score, defined as the Frobenius product of the contact or interaction matrices). FIG. 4B: Histogram of PSSs for these interfaces calculated either without B-factor weighting (n=0) or with high B-factor residues down-weighted (n=3) as described in the text. FIG. 4C: Histogram of unweighted PSSs (packing similarity score, defined as the Frobenius product of the contact or interaction matrices) for non-proper interfaces formed by proteins with different levels of sequence identity.

FIGS. 5A-5D are graphical representations of summary statistics on all interfaces in 39,208 protein crystal structures in the PDB.

FIG. 5 (A) is a histogram showing distributions of the fraction of residues participating in inter-protein packing contacts.

FIG. 5(B) is a histogram showing number of interfaces per crystal.

FIG. 5 (C) is a cumulative distribution graph showing fraction of interfaces equal to or smaller in size than the number indicated on the abscissa. In this graph, residues from the two interacting molecules are counted separately. The curve labeled “Largest” shows data for the single largest non-proper interface in each crystal.

FIG. 5(D) is aumulative size and range distributions for hierarchically defined packing elements (counting residues from one of the interacting molecules).

FIG. 6 shows a schematic overview of statistical methods and epitope-engineering software.

FIG. 7 shows a bar graph of the fraction of residues in loops, sheets, and alpha helices that interact in EBIEs. Fractions are shown for all residues, only residues that are surface-exposed or buried, as calculated by DSSP, or all residues interacting in BioMT interfaces only.

FIGS. 8A-8C illustrate improvement of crystallization of an integral membrane protein via epitope engineering.

FIG. 8(A) is a schematic summary of the results from a representative initial crystallization screen at 20° C.

FIG. 8(B) is a micrograph of one well of excellent lead crystals obtained for the MD-to-AG mutant protein in this screen.

FIG. 8 (C) is the same well as FIG. 8(B) from a wild-type screen conducted in parallel.

FIG. 9 shows epitope-engineering of proteins giving intractable crystals.

FIGS. 10A-10F show the results from preliminary epitope-engineering experiments. 36 single epitope mutations were designed in nine proteins. Subsequently, pairs or triplets of these were combined to make five proteins bearing multiple epitope mutations. These 41 protein variants harboring single and multiple epitope mutations were purified and screened for crystallization using the NESG pipeline. FIG. 10A: Differences in soluble yield in E. coli compared to corresponding WT protein, as scored on a standard 0-5 scale³³. FIG. 10B: Ratio of crystallization stock concentrations compared to WT protein. FIG. 10C: Difference in Thermofluor T_(m) for 30 single mutants. FIG. 10D: Change in number of crystallization hits compared to WT four weeks after set up in the 1536-well robotic screen at the Hauptman-Woodward Institute. FIG. 10E: Number of unique crystallization conditions in this screen in which the epitope mutant gave a hit while the WT did not. FIG. 10F: Crystal-packing contact involving the mutated F39R residue in the 1.8 Å crystal structure of NESG target BhR182

FIGS. 11A-11B show the relationship of calculated residue interaction energies in MEDUSA and packing similarity score (PSS). FIG. 11A: Scatterplot of calculated interfacial interaction energy for each residue versus its individual PSS in comparing interfaces from crystal structures of proteins with ≥98% sequence identity. These data come from interfaces between 40-60 residues in size (counting residues from both interacting chains); equivalent data were obtained for interfaces down to 7 residues in size. The dotted trendline represents the results of a linear regression analysis. FIG. 11B: Residue-specific interfacial interaction energy distributions for individual residues with PSSs less than 0.1 (red) or from 0.1-1.0 (black).

FIGS. 12A-12I show redundancy-adjusted number of counts for Interface, FBIE, and EBIE.

FIG. 12A shows redundancy-adjusted number of counts/area for Interface.

FIG. 12B shows redundancy-adjusted number of counts/number of residues for Interface.

FIG. 12C shows redundancy-adjusted number of counts/spread for Interface.

FIG. 12D shows redundancy-adjusted number of counts/area for FBIE.

FIG. 12E shows redundancy-adjusted number of counts/number of residues for FBIE.

FIG. 12F shows redundancy-adjusted number of counts/spread for FBIE.

FIG. 12G shows redundancy-adjusted number of counts/area.

FIG. 12H shows redundancy-adjusted number of counts/number of residues for EBIE.

FIG. 12I shows redundancy-adjusted number of counts/spread EBIE.

FIG. 13 shows a solubility comparison of VCR193 single mutants.

FIG. 14 shows a solubility comparison of VCR193 multi mutants.

FIG. 15 shows that epitope mutations open up a new dimension in exploration of crystallization space. The first number in each diagonal cell shows the total number of conditions in which crystals (“hits”) were observed for each protein variant. The numbers in parentheses in these cells indicate the number of unique chemical conditions giving hits for that variant compared to, first, the WT protein and, second, all other mutant variants evaluated. The off-diagonal cells show the number of hit conditions for the variants on the row and the column that were not shared with one another (i.e., first for the protein on the row and second for the one on the column).

FIG. 16 shows the results of an epitope-engineering study on four “no hits” proteins, i.e., proteins that yielded no crystallization hits in two independent screens of the protein with wild type sequence. The results show that crystal structures were solved for two of these four proteins using 4-5 single eptitope mutations per protein.

FIG. 17 shows the structure of epitope-engineered protein LpYceA (LgR82). The eptitope mutation that produced this structure participates directly in a crystal-packing interaction.

FIG. 18 shows “surface-shaping” to calibrate expectations for participation in crystal-packing interactions.

FIG. 19 shows that Arg in alpha-helices is the most strongly overrepresented amino-acid/secondary-structure class in interfaces in the PDB.

FIG. 20 shows polar amino acids predominate those most strongly overrepresented in interfaces after area-normalization.

FIG. 21 shows single amino acid mutations do not solve the crystallization issue that about one third of naturally occurring proteins have surface epitopes that promote solubility while having high crystal-packing potential.

FIGS. 22A-22B show that some crystallization-enhancing epitope mutations do not alter “solubility” in (NH4)2SO4 or PEG. FIG. 22A: MaR262 solubility in the presence of NH4SO4. FIG. 22B: MaR262 solubility in the presence of PEG3350.

FIGS. 23A-23B show that epitope mutations generally decouple “crystallizability” from thermodynamic “solubility” and that some epitope mutations increase “solubility” in (NH4)2SO4 while decreasing it in PEG. FIG. 23A: ER40 solubility in the presence of NH4SO4. FIG. 23B: ER solubility in the presence of PEG3350.

FIGS. 24A-24B show the lower “solubility” in PEG of some epitope mutants may be due to enhanced “crystallizability.” FIG. 24A: Solubility of LgR82 solubility in the presence of NH4SO4. FIG. 24B: LgR82 solubility in the presence of PEG3350.

FIGS. 25A-25B show other epitope mutations increasing “crystallizability” also increase “solubility” in PEG and that epitope engineering can decouple “crystallizability” from thermodynamic “solubility.” FIG. 25A: Solubility of VpR106 solubility in the presence of NH4SO4. FIG. 25B: VpR106 solubility in the presence of PEG3350.

DETAILED DESCRIPTION OF THE INVENTION

The issued patents, applications, and other publications that are cited herein are hereby incorporated by reference to the same extent as if each was specifically and individually indicated to be incorporated by reference. The contents of International Application No. PCT/US2011/33135; U.S. Provisional Patent Application No. 61/325,723; U.S. Provisional Patent Application No. 61/432,901 and U.S. application Ser. No. 13/694,010 are incorporated by reference in their entireties.

Research on the crystallization of proteins substantially predated efforts to determine their atomic structures using diffraction methods. Despite the historical importance of avidly crystallizing proteins, most proteins do not produce high-quality crystals. Even for proteins with the most promising sequence properties, at most ⅓ yield crystal structures from a single construct. These include the development of efficacious chemical screens that mimic historically successful crystallization conditions, sophisticated robots that enable more crystallization conditions to be screened with less protein and effort, and numerous innovations that improve crystallization in some cases. However, as long as most proteins cannot be crystallized, crystallization fundamentally remains a hit-or-miss proposition.

Existing methods for improving protein crystallization work with limited efficiency. Consistent with this premise, changes in primary sequence have been demonstrated to alter substantially the crystallization properties of many proteins. Disordered backbone segments can be identified using elegant hydrogen-deuterium exchange mass spectrometry methods, and constructs with such segments excised have shown improved crystallization properties. Progressive truncation of the N- and C-termini of the protein can also yield crystallizable constructs of proteins that initially failed to crystallize. However, many nested truncation constructs generally need to be screened, sometimes with termini differing by as little as two amino acids; even after extensive effort, this procedure still frequently fails to yield a soluble protein construct producing high-quality crystals. The Surface Entropy Reduction (SER) method uses site-directed mutagenesis to replace high-entropy side chains on the surface of the protein (generally lys, glu, and gln) with lower entropy side chains (generally ala). In most cases in which a substantial improvement in crystallization has been obtained by this method, a pair of mutations was introduced at adjacent sites. While some successes have been obtained, most such mutations reduce the solubility of the protein, frequently so severely that it prevents effective protein purification.

Analyses of large-scale experimental studies show that the surface properties of proteins, and particularly the entropy of the exposed side chains, are a major determinant of protein crystallization propensity⁴. Such studies demonstrated that overall thermodynamic stability is not a major determinant of protein crystallization propensity. They also identified a number of primary sequence properties that correlate with crystallization success, including the fractional content of several individual amino acids (i.e., gly, ala, and phe). Equivalent methods have been used to assess correlations between protein sequence properties and expression/solubility results (Price et al., 2011, Microbial Informatics and Experimentation, 1:6, doi:10.1186/2042-5783-1-6). These studies demonstrated that the individual amino acids that positively correlate with crystallization success negatively correlate with protein solubility, and vice versa. This effect severely limits the efficacy of single amino acid substitutions in improving protein crystallization because crystallization probability is low unless starting with a monodisperse soluble protein preparation. Therefore, more sophisticated approaches than single amino-acid substitutions are needed for efficient engineering of improved protein crystallization.

The methods described herein related to methods for improving protein crystallization by the introduction of complex sequence epitopes that mediate high-quality packing contacts in crystal structures deposited into the Protein Data Bank (PDB).

In certain aspects, the invention relates to the finding that many naturally occurring proteins have excellent solubility properties and also crystallize very well. In certain aspects, the invention relates to the finding specific protein surface epitopes that can mediate strong interprotein interactions under the conditions that drive protein crystallization without compromising solubility in the dilute aqueous buffers used for purification. Described herein are such epitopes as well as methods for finding such epitopes and using them to engineer crystallization of otherwise crystallization-resistant proteins. In certain aspects, the invention described herein relates to linear sequence epitopes contributing to interface formation in existing protein crystal structures. The methods described herein can be used to rank the packing quality and potential of these epitopes based on statistical analyses of epitope prevalence and properties combined with molecular-mechanics analyses of interfacial and intramolecular packing energies. Such rankings can be used to prioritize epitopes for systematic experimental evaluation of their potential to improve the crystallization properties of otherwise crystallization-resistant proteins.

As used herein, the recitation of a numerical range for a variable is intended to convey that the invention may be practiced with the variable equal to any of the values within that range. Thus, for a variable that is inherently discrete, the variable can be equal to any integer value within the numerical range, including the end-points of the range. Similarly, for a variable that is inherently continuous, the variable can be equal to any real value within the numerical range, including the end-points of the range. As an example, and without limitation, a variable which is described as having values between 0 and 2 can take the values 0, 1 or 2 if the variable is inherently discrete, and can take the values 0.0, 0.1, 0.01, 0.001, or any other real values ≥0 and ≤2 if the variable is inherently continuous.

As used herein, unless specifically indicated otherwise, the word “or” is used in the inclusive sense of “and/or” and not the exclusive sense of “either/or.”

The singular forms “a,” “an,” and “the” include plural references unless the content clearly dictates otherwise. Thus, for example, reference to “an epitope” includes a plurality of such epitopes.

An “epitope,” as used herein, is as a specific sequence of amino acids with a specific secondary-structure pattern that makes intermolecular packing contacts. The term “epitope” includes a “sub-epitope” which is also called an “epitope subsequence” herein. In some embodiments, the term “epitopes” encompasses Elementary Binary Interaction Epitopes (EBIEs).

An “epitope subsequence” or a “sub-epitope”, as used herein, is a sequence within an “epitope”, i.e., within a specific pattern of amino acids with a specific secondary-structure pattern that makes intermolecular packing contacts. For example, the ExxxR/HHHHH epitope subsequence contains Glu and Arg making packing contacts at positions four residues apart in a continuous segment of α-helix.

The term “polar amino acid” includes serine (Ser), threonine (Thr), cysteine (Cys), asparagine (Asn), glutamine (Gln), histidine (His), lysine (Lys), arginine (Arg), aspartic acid (Asp), and glutamic acid (Glu).

The term “hydrophobic amino acid” includes glycine (Gly), alanine (Ala), valine (Val), leucine (Leu), isoleucine (Ile), proline (Pro), phenylalanine (Phe), methionine (Met), tryptophan (Trp), and tyrosine (Tyr).

As used herein, EBIE(s) refers to Elementary Binary Interaction Epitope(s), CBIE refers to Continuous Binary Interaction Epitopes(s), and FBIE(s) refers to Full Binary Interaction Epitope(s).

In certain aspects, the methods described herein are based on a new approach to engineering improved protein crystallization based on introduction of historically successful crystallization epitopes and sub-epitopes into crystallization-resistant proteins. In certain aspects, the methods described herein relate to the results of data mining high-throughput experimental studies. This analysis showed that crystallization propensity is controlled primarily by the prevalence of low-entropy surface epitopes capable of mediating high-quality crystal-packing interactions. The PDB contains an archive of such epitopes in deposited crystal structures; however, other databases can be used according to the methods described herein. Computational methods can be used in connection with the methods described herein to identify and analyze all crystal-packing epitopes in the PDB. In certain aspects, the invention relates to metrics useful for ranking the efficacy of packing epitopes in order to identify those with a high probability of forming energetically favorable interactions under the low water-activity conditions used to drive crystallization. For example, such metric can include, but are not limited to statistical over-representation of each epitope in packing interactions with diverse partner sequences in the PDB. However, other ranking strategies are suitable for use with the methods described herein, including, but not limited to, using molecular mechanics calculations to estimate inter-molecular packing energy. In certain aspects, the methods described herein can be used to engineer the surface of a protein to be enriched in epitopes with favorable packing potential that will promote formation of a well-ordered 3-dimensional lattice. When the packing interfaces in some regular lattice have favorable free energy, the formation of that lattice is favored thermodynamically due to the consistent gain in energy for every added molecule. Thus, in certain aspects the invention described herein relates to the prevalence of surface epitopes with high propensity to form such favorable interactions, which will influence whether a protein can find a lattice structure with favorable intermolecular interactions or whether it precipitates amorphously with heterogeneous interactions. In certain aspects, the invention relates to the finding that increasing the prevalence of surface epitopes with favorable packing potential increases high quality crystallization.

Generation of a Library of Epitopes that are Expected to Improve Crystallization Properties of a Target Protein

In some embodiments, a database is generated containing a library of all elementary, continuous, or full binary interaction epitopes (EBIEs, CBIEs, and FBIEs) in the PDB that span at most two successive regular secondary structural elements and flanking loops (as identified by the DSSP algorithm (Kabsch and Sander, Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22 (12), 2577-637(1983)).

An interface is defined as all residues making atomic contacts (≤4 Å) between two protein molecules related by a single rotation-translation operation in the real-space crystal lattice. The interface is decomposed into features called Elementary Binary Interaction Epitopes (EBIEs). These comprise a connected set of residues that are covalently bonded or make van der Waals interactions to one other in one molecule and that also contact a similarly connected set of residues in the other molecule forming the interface. EBIEs can be the foundation of this analysis because these features and their constituent sub-features represent potentially engineerable sequence motifs. One or more EBIEs that are connected to one another by covalent bonds or van der Waals interactions within a molecule form a Continuous Binary Interaction Epitope (CBIE). One or more CBIEs in one molecule that are connected to one another indirectly by a chain of contacts across a single interface form a Full Binary Interaction Epitope (FBIE). The set of one or more FBIEs that all mediate contacts between the same two molecules in the real-space lattice form a complete interface.

The sequence of both contacting and non-contacting residues is stored along with the standard DSSP-encoding of the secondary structure at each position in the protein structure in which the epitope was observed to mediate a crystal-packing interaction. All metrics possibly related to the crystal-packing potential of the epitope are recorded, including B-factor distribution parameters, statistical enrichment scores relative to all interfaces in the PDB, as well as conservation in multiple crystals from homologous proteins, and crystallization propensity and solubility scores based on the sequence composition of the epitope. The database includes the identity of all EBIE pairs making contact with each other as well as a breakdown of the composition of all FBIEs and CBIEs in terms of their constituent EBIEs. This versatile resource for analyzing and engineering crystallization epitopes is available on the crystallization engineering web-server.

One embodiment of the invention which demonstrates how an epitope library can be generated is schematized in FIG. 1. A hierarchical analytical scheme has been developed to identify contiguous epitopes potentially useful for protein engineering, and has been used to analyze all inter-protein packing interactions in crystal structures in the PDB. The hierarchical scheme can be very useful for this analysis.

The PDB contain some structures that have errors which creates inaccuracies in the characterization of these structures. It also contains many structures that are partially or completely redundant that create problems in the eventual identification of sequence motifs that are over-represented in crystal-packing interactions. These concerns can be addressed by computational flagging and down-weighting mechanisms, respectively.

Biological and non-biological protein oligomers can be addressed as follows. To identify biological oligomers, the BioMT database (Krissinel and Henrick, Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372, 774-797), which attempts to categorize all previously described biological interfaces in the PDB, can be used. Interfaces so identified are flagged as “BioMT” interfaces. Recognizing that some oligomeric interfaces may not be appropriately categorized by BioMT, the set of “proper” interfaces which could be either biological or crystallographic are identified.

Interfaces are designated as “proper” if they form part of a regular oligomer with proper rotational symmetry (i.e., n protein molecules in the real-space lattice each related to the next by a 360°/n rotation±5°, with n being any integer from 2-12) and “non-proper” if they do not. Proper interfaces could potentially be part of a stable physiological oligomer while non-proper interfaces cannot. After these two categorization steps, four sets of interfaces exist: the set of all interfaces; the set of biological interfaces identified by BioMT; the set of proper interfaces not identified as biological interfaces by BioMT, but which could potentially be either biological or crystallographic; and the set of interfaces which are not identified by BioMT and which are not proper, as defined above. The most conservative approach to isolating non-physiological crystal-packing interactions is to focus exclusively on non-proper interfaces in order to exclude any complex that is potentially a physiological oligomer. Nonetheless, epitopes that contribute to stabilizing physiological oligomers may still be useful for engineering purposes, and epitopes that promote formation of a regular oligomer would be particularly useful because stable oligomerization strongly promotes crystallization (Price et al., Understanding the physical properties that control protein crystallization by analysis of large-scale experimental data. Nat Biotechnol 27 (1), 51-7 (2009)).

FIGS. 2A-2I illustrate characteristics of oligomeric vs. crystal-packing interfaces. Distributions are shown for three levels of interaction classification: half-interfaces (A, B, and C), full binary interaction epitopes (D, E, and F), and elementary binary interaction epitopes (G, H, and I). Distributions show the number of counts of the relevant element binned by buried surface area (A, D, and G), number of participating residues (B, E, and H), and spread—the number of residues, interacting or not, spanned by the element (C, F, and I). Within each graph, separate distributions are shown for all elements, elements which appear in the BioMT database of biological oligomers, elements which do not appear in BioMT but are within proper interfaces (as defined above), and elements which do not appear in BioMT and are not proper interfaces. All counts are redundancy-culled as described below. PSS is the Packing Similarity Score, and can be calculated as discussed further below.

One approach to redundancy reduction of epitope counts is described herein. Starting with all interfaces (FIG. 3) found in the analyzed set of 39,208 crystal structures, select all non-pathological protein crystals based on exclusion of those with pathologically close intermolecular packing.

Cull-1: Select non-redundant crystals: PSS<0.5 for any pair of crystals (comparing all chains).

Cull-2: Select non-BioMT interfaces, i.e., not related by PDB-designated BioMT transformation.

Cull-3: Select non-redundant interfaces within each crystal, i.e., with PSS<0.5 for any pair of interfaces within each crystal.

Cull-3′: Select non-redundant interfaces between crystals, i.e., with PSS<0.5 for any pair of interfaces included in the analyses, even those in different crystals.

Count unique chain sequences contributing to Cull-3 at the 25% identity level (i.e., the number of protein chains without any pair having greater than or equal to 25% identity to one another).

Even when all biological and oligomeric interfaces are removed from the dataset, significant redundancy remains within the PDB. Many proteins in the PDB have had multiple crystal structures deposited, which may have very similar if not identical packing interactions (e.g., multiple mutations at a non-interacting active site) but which can also have completely separate packing interactions (e.g., crystallization under different conditions into a different crystal form). Simply culling identical or homologous proteins would remove all redundancy but would also eliminate significant information from the second situation, where the same protein forms crystals with different packing interactions.

To implement a redundancy down-weighting, the Packing Similarity Score (PSS) has been developed to evaluate the similarity between inter-protein interfaces, full chain interactions, and crystals. PSS can be calculated in the following way: Interactions matrices are generated for each interface, with rows representing residues in one chain and columns representing residues in the other chain. Cells in the matrix include the number of inter-atomic contacts between the two residues (including contacts mediated by a single solvent molecule) and the B-factor-derived weight associated with that contact. The PSS between two interfaces is defined as the normalized Frobenius product (a matrix dot-product) of the two interaction matrices, which are aligned to one another based on standard methods for aligning homologous protein sequences, as described below. The PSS takes values in the range between 0 and 1. This value contains significant information about the overall similarity of two interfaces, and is sensitive to small changes (FIG. 4A). To calculate the PSS for two chains or two crystals, the process is essentially repeated on a larger scale. Each interface in one chain is matched with an interface in the second chain with which it has the highest PSS. Interfaces are ordered in this way, and the individual interaction matrices are then inscribed into the larger chain/chain or crystal/crystal interaction matrix. The Frobenius product of this matrix is then taken. However, since best-matches are not necessarily reciprocal, the best-interface-matching process is repeated in reverse to ensure reciprocity of the chain or crystal PSS. The Frobenius products of the two matrices are added and then normalized to give the chain or crystal PSS.

Each interface in a crystal structure is quantitatively described by a contact matrix C containing the corresponding C_(ij) values (i.e., with its rows and columns indexed by the residue numbers in the two interaction proteins). To evaluate the similarity in inter-protein interfaces formed by homologous proteins, their sequences are aligned using CLUSTAL-W (Higgins et al., Using CLUSTAL for multiple sequence alignments. Methods in Enzymology 266, 383-402 (1996)) after transitively grouping together all proteins sharing at least 25% sequence identity. This procedure effectively aligns both the columns and rows in the contact matrices for interfaces formed by the homologous proteins. The Packing Similarity Score (PSS) between the interfaces is then calculated as the Frobenius (matrix-direct) product between the respective contact matrices. This procedure is mathematically equivalent to calculating a dot-product between vectors filled with the contact count between corresponding residue pairs in homologous interfaces. PSS values range from 1.0, if the number of contacts between each interfacial residue pair is identical, to 0.0, if no pairwise contacts are preserved.

FIG. 5A-5D show statistics from application of the analytical scheme shown in FIG. 3 to all crystal structures in the PDB (39,208 entries). The average number of total, proper, and non-proper interfaces per protein molecular are 6.9, 1.8, and 5.1, respectively (FIG. 5A). While a minimum of four interfaces is required for a single molecule to form a 3-dimensional lattice, fewer are possible when multiple molecules are present in the crystallographic asymmetric unit. Proteins generally contain only a small number of interfaces beyond the minimum required for lattice formation, indicating that most interfaces contribute to structural stabilization of the lattice. On average, 50% of surface-exposed residues and 36% of all residues participate in inter-protein packing interactions (FIG. 5B). While interfaces range widely in size, 36% of all interfaces and 42% of non-proper interfaces contain 10 or fewer residues counting contributions from both sides of the interface (˜5 from each participating molecule) (FIG. 5C). The small size of the average interface is encouraging relative to the feasibility of engineering interface formation. Half of all interfaces are under eight residues in size, and a quarter (8678 total in the dataset analyzed herein) are under eight residues in range within the polypeptide chain (separation). The cumulative size/range distributions for all interfaces, CBIEs, and EBIEs (FIG. 5D) shows that most interfaces are topologically simple and local in the primary sequence, even though some are complex. It is noteworthy that FBIEs contain on average fewer than two EBIEs and that most EBIEs are less than 4 residues in size and 10 residues in range. These small EBIEs represent prime candidates for engineering improved crystallization of crystallization-resistant proteins.

The epitope library was used to count all EBIEs that appear in the PDB, and to determine which sequences are statistically over-represented in EBIEs given their background frequency in non-interacting sequences in the PDB. Before specific amino acid sequences were considered, the secondary structure patterns that appeared most frequently in EBIEs were examined. Some secondary structure patterns appeared much more frequently than others; these are summarized in Table 1.

TABLE 1 SECONDARY STRUCTURE MOTIFS IN EBIEs^(a) Null Secondary Fraction Fraction Probability Probability Size Structure in PDB in EBIEs in EBIE in EBIE Z Score P-value* 1 C 0.41 0.510 0.357 0.33 85.2 0 1 H 0.36 0.332 0.321 0.33 −33.8 3.21E−251 1 E 0.23 0.159 0.290 0.33 −91.3 0 2 CC 0.32 0.481 0.171 0.15 101.5 0 2 HC 0.036 0.048 0.168 0.15 29.1 1.51E−186 2 CH 0.035 0.042 0.154 0.15 9.5 6.95E−22  2 EC 0.049 0.042 0.151 0.15 4.8 7.29E−07  2 CE 0.050 0.046 0.144 0.15 −4.2 1.65E−05  2 HE 0.0016 0.00061 0.118 0.15 −5.5 2.70E−08  2 EH 0.0029 0.0012 0.091 0.15 −16.9 5.60E−64  2 EE 0.184 0.106 0.134 0.15 −31.3 1.84E−215 2 HH 0.320 0.232 0.116 0.15 −113.7 0 3 HCC 0.031 0.051 0.096 0.076 35.8 2.51E−280 3 CCH 0.029 0.042 0.094 0.076 30.4 1.10E−203 3 CCC 0.245 0.436 0.094 0.076 98.0 0 3 CHH 0.035 0.057 0.092 0.076 31.2 1.42E−214 3 ECC 0.043 0.052 0.090 0.076 27.2 1.33E−162 4 HCCH 0.0025 0.0040 0.057 0.042 9.4 4.30E−21  4 HCHH 0.0026 0.0044 0.057 0.042 9.6 4.55E−22  4 HCCC 0.026 0.046 0.056 0.042 30.0 7.12E−198 4 CCCH 0.023 0.039 0.056 0.042 27.3 2.22E−164 4 CECH 0.00083 0.00077 0.055 0.042 3.7 0.000142 ^(a)Table 1 shows the secondary structure motifs (coil [C], strand [E], or helix [H]) most over-represented in EBIEs. Full distributions are shown for sequences of length 1 and 2, and the 5 most over-represented (and statistically significant) sequences of length 3 and 4. The table shows the frequency of that motif in the PDB generally, the frequency in EBIEs, the probability of any given instance of that motif participating in an EBIE, the null probability of any sequence or of that length participating in an EBIE, and the Z-score and P-value of that over- or under-representation. All calculations were done on the weighted set of chains. *-P-values denoted 0 fell below the computational threshold of Microsoft Excel, and are therefore less than 10⁻³⁰⁰.

Next, amino acid sequences which appear as subsequences within EBIEs (e.g., an interacting trimer which makes up only part of an EBIE) were considered. Due to computational restrictions, the statistical analysis was only performed on dimers, trimers, and tetramers. Many of these short amino acid sequences are significantly over-represented in the set of EBIEs (Table 2).

TABLE 2 TOP SEQUENCE MOTIFS IN EBIEs, IGNORING SECONDARY STRUCTURE.^(a) Null Fraction in Fraction in Probability Probability Size Sequence PDB EBIEs in EBIE in EBIE Z Score P-value* 2 HH 0.00109 0.00032 0.30 0.15 32.9 5.43E−238 2 WC 9.48E−05 2.26E−05 0.24 0.15 5.9 2.10E−09  2 CH 0.00037 8.04E−05 0.22 0.15 9.1 6.03E−20  2 HM 0.00051 0.00011 0.21 0.15 10.2 8.33E−25  2 CS 0.00070 0.00015 0.21 0.15 11.1 4.95E−29  3 SCW 5.35E−06 4.69E−06 0.88 0.076 16.6 1.01E−25  3 HHH 0.00033 0.00011 0.33 0.076 42.3 0 3 WCG 1.87E−05 6.26E−06 0.33 0.076 10.0 3.96E−23  3 SHM 8.78E−05 2.29E−05 0.26 0.076 15.6 2.13E−54  3 VAC 3.48E−05 8.11E−06 0.23 0.076 8.3 1.32E−16  4 CSAG 1.55E−05 6.55E−11 1.26 0.042 21.8 1.56E−29  4 TQWC 1.79E−06 7.58E−12 0.98 0.042 11.5 7.42E−09  4 HCGV 5.29E−06 2.23E−11 0.80 0.042 12.3 5.04E−10  4 ACNG 2.96E−06 1.25E−11 0.80 0.042 11.1 6.40E−09  4 DACQ  6.9E−06 2.92E−11 0.79 0.042 12.6 4.18E−11  ^(a)Table 2 shows the amino acid sequences most over-represented in EBIEs, ignoring secondary structure. The top five most over-represented (and statistically significant) examples are shown for sequences of length 2, 3, and 4. The table shows the frequency of that motif in the PDB generally (weighted by surface-interior proclivity to match the surface-interior distribution of EBIEs, as described above), the frequency in EBIEs, the probability of any given instance of that motif participating in an EBIE, the null probability of any sequence of that length participating in an EBIE, and the Z-score and P-value of that over- or under-representation. All calculations were done on the weighted set of chains. *-P-values denoted 0 fell below the computational threshold of Microsoft Excel, and are therefore less than 10⁻³⁰⁰.

Finally, it was determined which complete EBIE sequences appeared significantly more frequently than their background frequency would suggest (Table 3).

TABLE 3 TOP SEQUENCE MOTIFS IN EBIEs, INCLUDING SECONDARY STRUCTURE.^(a) Null Secondary Fraction Fraction in Probability Probability Size Sequence Structure in PDB EBIEs in EBIE in EBIE Z Score P-value* 2 CW H  2.2E−05 1.01E−05 0.46 0.15 9.8 1.59E−22  2 HH CC 0.00060 0.00023 0.38 0.15 39.0 0 2 WC CC 3.75E−05 1.37E−05 0.37 0.15 9.0 3.82E−19  2 HM CC 0.00022 7.21E−05 0.32 0.15 17.5 2.31E−68  2 GK CH 0.00029 8.05E−05 0.28 0.15 14.8 2.31E−49  3 PTW CEE 2.17E−06 2.35E−06 1.08 0.076 12.2 5.03E−14  3 CAT ECC 1.94E−06 1.96E−06 1.01 0.076 11.5 5.15E−12  3 VAC ECC 7.11E−06 7.16E−06 1.01 0.076 22.1 5.11E−44  3 GSC CCH 3.19E−06 2.96E−06 0.93 0.076 13.6 5.11E−17  3 VGK CCH 1.56E−05 1.33E−05 0.85 0.076 27.5 4.72E−164 4 AGKT CCHH 1.43E−05 6.04E−11 2.12 0.042 19.6 5.89E−24  4 VGKS CCHH 2.49E−05 1.05E−10 1.39 0.042 27.5 1.88E−45  4 GNLA CCCE 1.97E−06 8.33E−12 1.33 0.042 13.0 3.81E−10  4 QGLG CCHH  1.2E−06 5.08E−12 1.33 0.042 11.6 5.84E−09  4 AAGK CCCH 5.92E−06  2.5E−11 1.31 0.042 16.9 6.53E−17  ^(a)Table 3 shows the amino acid sequences most over-represented in EBIEs, considering secondary structure. The top five most over-represented (and statistically significant) examples are shown for sequences of length 2, 3, and 4, where the sequence is considered to be the combination of residue identity and secondary structure (coil [C] , strand [E], or helix [H]) for that position, as calculated by DSSP. The table shows the frequency of that motif in the PDB generally (weighted by surface-interior proclivity to match the surface-interior distribution of EBIEs, as described above), the frequency in EBIEs, the probability of any given instance of that motif participating in an EBIE, the null probability of any sequence of that length participating in an EBIE, and the Z-score and P-value of that over- or under-representation. All calculations were done on the weighted set of chains. *-P-values denoted 0 fell below the computational threshold of Microsoft Excel, and are therefore less than 10⁻³⁰⁰.

As of the time of the analysis presented herein, among the PDB protein chains there were 54,317,358 potential epitope subsequences of length 2 to 6. The substrings describe primary and secondary structure and are of forms like FxGH CcCH, i.e., intermediate amino acid letters masked by x's are ignored but their secondary structure is still considered. There are 31 such masks total. Not every possible permutation of 20 amino acids and 3 structure codes among the 31 masks (57,625,347,600 total) is found in the PDB. Accordingly, 54,317,358 is the number of independent trials for purposes of Bonferroni correction for multiple-hypothesis testing. Therefore, the 5% significance threshold becomes 9.205e-10 after dividing by the number of independent tests.

In some embodiments, all epitope subsequences that make up the final library have an over-representation-in-interfaces P-value below the afore mentioned significance threshold. In some embodiments, the sequence's redundancy-weighted “in epitopes” and “in prior” counts are at least 10 (in order to deprioritize the few epitopes with very low counts that still manage to remain significant). In some embodiments, the fraction of redundancy-corrected occurrences of the epitope having non-water bridging solvent molecules is no more than 50% of the total such count, and the sequence's over-representation ratio (redundancy-corrected count in epitopes/expected redundancy-corrected count in epitopes) is at least 1.5. The number of epitopes that meet these four criteria is 2,040. They make up one embodiment of an epitope subsequence library for use in crystallization engineering.

Tables 4-35 (in Appendix A) provide a list of 100 top patterns (engineering candidates) for epitopes in each of 32 interaction pattern classes. Column “Sequence” provides the amino acid sequence of the epitope subsequence (Tables 5-35) or of a single amino acid (Table 4). Lower case ‘x’ means that that the amino acid identity of the residue at that position has not been explicitly considered. Column “Structure” shows the observed secondary structure motifs (loop or coil [C], beta strand [E], or helix [H]) of the pattern. All measured frequencies of occurrence were redundancy-corrected. Column “In Epitopes” represents the observed number of occurrences of each epitope in the PDB. Column “Expected in Epi” represents the expected number of each epitope in crystal-packing interfaces in the PDB. Column “In PDB” represents the total number of times the epitope's sequence appears in the PDB, regardless of whether or not it participates in interactions. Column “Z-score” represents the number of standard deviations that the observed count is away from the expected count. P-values represent the upper and the lower tail integrals of the binomial distribution. Column “Distribution” represents whether the distribution is approximated as normal (N) or as exact binomial (B). The “Observed ratio” is the fraction of “In PDB” that actually makes crystal-packing contacts. “Null probability” is the fraction of “In PDB” expected in crystal-packing epitopes. All calculations were done on the weighted set of chains. *-P-values denoted 0 fell below the lowest floating point precision value, and are therefore at least less than 10⁻³⁰⁰.

Table 36 (in Appendix A) provides a list of epitopes subsequences according to some embodiments of the invention. In Table 36, “Num Crystal Sets” is the number of crystals in the PDB containing the epitope subsequence after correction for redundancy in overall packing using PSS. “Num Interface Intersets” is the number of interfaces in the PDB containing the epitope subsequence after correction for redundancy in overall packing using PSS. “Num Chainsets 25” is the number of sequence-unique proteins (<25% identity between any pair) in the PDB containing the epitope subsequence. “Non-Water Solvent” is the fraction of epitopes containing the epitope subsequence whose contacts to the partner epitope across the crystal-packing interface involve bridging interactions via ligands bound to the protein or via small molecules from the crystallization solution other than water. The details for Table 37 is provided further below.

Surprisingly, many epitopes in Tables 2-3 and 5-37 include polar residues. Epitopes with polar residues are advantageous as they are less likely to cause the modified protein to become insoluble.

In some embodiments, the epitope library comprises the epitopes in Tables 5-37. In some embodiments, the epitope library comprises at least 100, at least 200, or at least 300 epitopes from the list of epitopes in Tables 2-3 and 5-37.

Computational Methods for Modifying Protein Sequences to Improve their Crystallization

Methods for modifying protein amino acid sequences to improve crystallization properties of the protein can be implemented on a server (in some instances referred to herein as the “protein engineering” server). In some embodiments, the server accepts a target protein sequence from a user and outputs one or more (in some embodiments several) protein sequences related to the target sequence, but having amino acid mutations that will improve crystallization of the target sequences. In general, the predicted secondary and tertiary structure of the target protein sequence is preserved in the modified protein.

One such embodiment of the method is described with reference to a protein engineering server described with reference to FIG. 6. In this embodiment, a user provides the amino acid sequence of the target protein to the server (the server receives the target protein sequence from the user). The server finds homologous protein sequences, for example using a program such as BLASTp, available through the National Center for Biotechnology Information (www.ncbi.nlm.nih.gov), and are described in, for example, Altschul et al. (1990), J Mol. Biol. 215:403-410; Gish and States (1993), Nature Genet. 3:266-272; Madden et al. (1996), Meth. Enzymol. 266:131-141; Altschul et al. (1997), Nucleic Acids Res. 25:33 89-3402); Zhang et al. (2000), J. Comput. Biol. 7(1-2):203-14.

The server then performs a multiple sequence alignment of the target sequence with the homologous protein sequences for example using a program such as CLUSTAL (Chenna et al., Multiple sequence alignment with the Clustal series of programs. Nucleic Acids Res 31(13):3497-500 (2003)). The server can also predict the structure of the target protein sequences, for example using a program such as PHD/PROF (Rost, B., PHD: predicting one-dimensional protein structure by profile-based neural networks. Methods in Enzymology 266, 525-539 (1996)). The epitope engineering part of the server takes one or more inputs selected from any combination of the target protein sequence, multiple sequence alignments, predicted secondary structure and the epitope subsequence library and provides a list of recommended mutations to improve protein crystallization. The output from the server can either be in the form of a list of mutations to be made in the target sequence or in the form of one or more amino acid sequences of the modified protein.

In some embodiments, multiple epitope subsequences are introduced in the amino acid sequence of the target protein simultaneously to provide a modified protein. For example, 1, 2, 3, 4, 5, or more epitope subsequences can be introduced into the same target protein to generate a modified protein.

In some embodiments, the engineering part of the server uses one or more of the following epitope prioritization criteria: over-representation P-value of the epitope subsequence in packing interfaces; fraction of occurrences of that epitope subsequence that make crystal-packing contacts in the PDB (i.e., that reside within EBIEs); frequency of occurrence of that epitope subsequence in the PDB database; sequence diversity of proteins containing that epitope subsequence in the PDB; sequence diversity of partner epitopes interacting with the corresponding epitope across crystal-packing interfaces in the PDB; absence of non-water bridging ligands in the crystal-packing interactions made by the corresponding epitopes in the PDB; lack of increase in hydrophobicity of the modified protein by introducing the epitope subsequence; or predicted influence of the epitope subsequence on the solubility of the modified protein. Each of the prioritization criteria can be assigned a different weight, including no weight. Any combination of these prioritization criteria can be used.

In some embodiments, an epitope subsequence that is over-represented by P-value of the epitope subsequence in the epitope subsequence library is a particularly suitable epitope subsequence for improving protein crystallization.

Fraction of epitope subsequence in crystal-packing contacts is the redundancy-corrected number of an epitope subsequence in crystal-packing contacts in the PDB divided by the redundancy-corrected total number of the epitope subsequence in the PDB. In some embodiments, an epitope subsequence for which a a high fraction of its occurrences in the PDB occur in crystal-packing contacts is a particularly suitable epitope for improving protein crystallization.

In some embodiments, an epitope with a high frequency of occurrence in the PDB is a particularly suitable epitope subsequence for improving protein crystallization. In some embodiments, an epitope subsequence that is present in proteins of diverse sequence in the PDB is a particularly suitable epitope subsequence for improving protein crystallization.

Partner epitopes are other epitopes contacted by an epitope in the PDB. In some embodiments, an epitope subsequence whose corresponding epitopes contact a diverse set of different epitopes in the PDB is a particularly suitable epitope for improving protein crystallization.

Non-water bridging ligands are non-protein molecules such as nucleotides and buffer salts. In some embodiments, an epitope subsequence whose corresponding epitopes frequently make contacts to partner epitopes via a non-water bridging ligand in the PDB is not a particularly suitable epitope subsequence for improving protein crystallization.

In some embodiments, an epitope subsequence that does not increase the hydrophobicity of the modified protein is a particularly suitable epitope subsequence for improving protein crystallization.

In some embodiments, an epitope subsequence that does not reduce the solubility of the modified protein is a particularly suitable epitope subsequence for improving protein crystallization. Solubility of a protein can be predicted, for example, using a computational predictor of protein expression/solubility (PES) was produced (available online at http://nmr.cabm.rutgers_edu:8080/PES/) (Price et al., 2011, Microbial Informatics and Experimentation, 1:6, doi:10.1186/2042-5783-1-6). Solubility can also be predicted as described in PCT/US11/24251, filed Feb. 9, 2011.

In some embodiments, the prioritized selection criterion is over-representation ratio, using a P-value cutoff. In some embodiments, the selection criteria are selected to prioritize mutations improving over-representation ratio at a given site (i.e., avoiding removing an epitope subsequence with a better ratio than the new epitope subsequence). In some embodiments, the selection criteria are selected to prioritize epitopes subsequence observed in packing interactions in at least 50 sequence-unrelated proteins (“chainsets”) in the PDB. In some embodiments, the selection criteria are selected to favor substitutions maintaining or increasing polarity over those reducing polarity.

The list of epitopes subsequence in the epitope subsequence library can be obtained from the comprehensive hierarchical analysis of the entirety of the PDB (several million epitopes total, the counts for each being redundancy-corrected), obtained for example as described below, which is then culled by the over-representation significance P-value against the Bonferroni-corrected 95% significance threshold. Epitopes subsequence can be discarded if they primarily participate only in solvent molecule-mediated bridging interactions involving molecules other than water, such as epitopes in nucleotide-binding motifs. Epitope subsequences can also be discarded if the total number of distinct protein homology sets that the corresponding epitopes appears in is too low, to ensure that the epitope's source structures have some variety.

In some embodiments, the resulting epitope subsequence library contains 1000-3000 epitopes. In some embodiments, the epitope subsequence library contains about 1000, about 2000, or about 3000 epitopes. In a specific embodiment, the epitope subsequence library contains about two-thousand epitopes.

In some embodiments, the epitope subsequences are 1-6 residues in size. In other embodiments, the epitope subsequences are 2-15 residues in size. Each epitope also has a secondary structure mask associated with it, for example, HHH, CCCC, HCCCH, ECCE, where H=helix, C=coli and E=beta strand.

In some embodiments, to generate mutation suggestions to improve crystallization for a protein of unknown structure, the method combines the epitope subsequence library, a secondary structure prediction by PHD/PROF, and a multiple sequence alignment of proteins homologous to the target. At every position in the target protein sequence, the method examines whether any one of the epitope subsequences from the epitope library can be introduced there through a change of a few amino acids. In some embodiments, a mutation at any one position is only allowed if the new amino acid can also be found at the same aligned position in one of the other homologous proteins. In some embodiments, “correlated evolution” metrics (Liu et al., Analysis of correlated mutations in HIV-1 protease using spectral clustering. Bioinformatics 2008, 24 (10), 1243-50; Eyal et al., Rapid assessment of correlated amino acids from pair-to-pair (P2P) substitution matrices. Bioinformatics 2007, 23 (14), 1837-9; Hakes et al., Specificity in protein interactions and its relationship with sequence diversity and coevolution. Proceedings of the National Academy of Sciences of the United States of America 2007, 104 (19), 7999-8004; Kann et al., Correlated evolution of interacting proteins: looking behind the mirrortree. J Mol Biol 2009, 385 (1), 91-8; Kann et al., Predicting protein domain interactions from coevolution of conserved regions. Proteins 2007, 67 (4), 811-20) can be used to deprioritize mutations anti-correlated with residue identity at other positions in the protein sequence to be mutated, which may be predictive of reduced stability of modified proteins.

In some embodiments, the secondary structure of the epitope subsequence to be inserted matches the predicted secondary structure (within some tolerated deviation). These criteria increase the probability that the mutations do not destabilize the target protein by introducing biophysically incongruent changes.

In some embodiments, there are approximately 100-300 epitope subsequences from the library that can be introduced at some position within the sequence in agreement with these guidelines.

In some embodiments, the epitope subsequences that are expected to improve crystallization of the target protein are sorted by their over-representation ratio in the PDB and presented to the researcher. The researcher can choose which and how many mutations to make, preferentially starting from the top of the list, depending on the available resources and specific peculiarities of the target protein.

Protein Engineering Server

The techniques, methods and systems disclosed herein may be implemented as a computer program product for use with a computer system or computerized electronic device. Such implementations may include a series of computer instructions, or logic, fixed either on a tangible medium, such as a computer readable medium (e.g., a diskette, CD-ROM, ROM, flash memory or other memory or fixed disk) or transmittable to a computer system or a device, via a modem or other interface device, such as a communications adapter connected to a network over a medium.

The medium may be either a tangible medium (e.g., optical or analog communications lines) or a medium implemented with wireless techniques (e.g., Wi-Fi, cellular, microwave, infrared or other transmission techniques). The series of computer instructions embodies at least part of the functionality described herein with respect to the system. Those skilled in the art should appreciate that such computer instructions can be written in a number of programming languages for use with many computer architectures or operating systems.

Furthermore, such instructions may be stored in any tangible memory device, such as semiconductor, magnetic, optical or other memory devices, and may be transmitted using any communications technology, such as optical, infrared, microwave, or other transmission technologies.

It is expected that such a computer program product may be distributed as a removable medium with accompanying printed or electronic documentation (e.g., shrink wrapped software), preloaded with a computer system (e.g., on system ROM or fixed disk), or distributed from a server or electronic bulletin board over the network (e.g., the Internet or World Wide Web). Of course, some embodiments of the invention may be implemented as a combination of both software (e.g., a computer program product) and hardware. Still other embodiments of the invention are implemented as entirely hardware, or entirely software (e.g., a computer program product).

Efficient Mutational Engineering of Protein Crystallization

The invention provides a new approach to engineering improved protein crystallization based on introduction of historically successful crystallization epitopes into crystallization-resistant proteins. Datamining the results of high-throughput experimental studies indicated that crystallization propensity is controlled primarily by the prevalence of low-entropy surface epitopes capable of mediating high-quality crystal-packing interactions (Price et al., Understanding the physical properties that control protein crystallization by analysis of large-scale experimental data. Nat Biotechnol 27 (1), 51-7 (2009)). The PDB contains a massive archive of such epitopes in deposited crystal structures.

In one embodiment, the invention provides methods for mutational engineering of crystallization that are efficient enough to enable the structure of any target protein to be determined with relatively modest effort compared to pre-existing methods.

The thermodynamics of crystallization have been analyzed extensively. If the individual packing interfaces in the lattice have favorable free energy, formation of a regular lattice is thermodynamically favored because of the consistent gain in energy for every added molecule. The prevalence of surface epitopes with high propensity to form such favorable interactions is likely to determine whether a particular protein can find a regular lattice structure with favorable intermolecular interactions or whether it precipitates amorphously with heterogeneous packing interactions. Increasing the prevalence of surface epitopes with favorable packing potential, as evidenced by participation in many interfaces in the PDB, can increase the probability of high quality crystallization.

Surface Entropy is a Determinant of Protein Crystallization Propensity

Results of large-scale experimental studies were analyzed to develop insight into the physical properties controlling protein crystallization. Statistical analyses were used to evaluate the relationship between protein sequence and successful crystal-structure determination (Price et al., Understanding the physical properties that control protein crystallization by analysis of large-scale experimental data. Nat Biotechnol 27 (1), 51-7 (2009)). The dataset comprised 679 biochemically well-behaved proteins that were taken through a consistent expression, purification, quality-control, and crystallization pipeline to yield 157 structures. Proteins yielding crystals of insufficient quality for structure determination were considered failures even if diffraction was observed, as occurred for 39 proteins. Retrospective analyses demonstrated that some key sequence features of these are more similar to proteins that failed to yield structures than those that did. Sequence properties that were analyzed included the frequency of each amino acid, mean hydrophobicity, mean side-chain entropy, a variety of electrostatic parameters, and the fraction of residues predicted to be disordered by the program DISOPRED2 (Ward et al., The DISOPRED server for the prediction of protein disorder. Bioinformatics 20 (13), 2138-9 (2004)). Logistic regressions were performed to evaluate the relationship between each of these continuous sequence parameters and the binary outcome of the crystallization/structure-determination effort. These analyses demonstrated that many sequence parameters are significantly predictive of outcome. However, multiple logistic regression and other analyses showed that most sequence effects are surrogates for side-chain entropy. Statistically independent contributions are made only by the predicted fraction of disordered residues (an inhibitory factor) and the fractional content of Ala, Gly, and possibly Phe residues (all positively correlated with success). Furthermore, we demonstrated that the side-chain entropy effect is localized to residues predicted to be surface exposed according to the PHD-PROF program (Rost, B., PHD: predicting one-dimensional protein structure by profile-based neural networks. Methods in Enzymology 266, 525-539 (1996)), which predicts both secondary structure and surface localization with ˜80% accuracy.

These analyses establish surface entropy as a major determinant of protein crystallization propensity. They also indicated that the Gly residues promoting successful crystallization are localized to short surface loops and likely to be at least partially buried in inter-protein packing interfaces.

Thermodynamic Stability is not a Major Determinant of Protein Crystallization Propensity

In the studies described herein, thermodynamic stabilities of a substantial subset of proteins in the crystallization dataset were measured. These studies showed a small advantage for hyper-stable proteins but equivalent crystallization propensity for proteins spanning the wide range of stability characteristic of the most proteins from mesophilic organisms. Therefore, thermodynamic stability is not a major determinant of protein crystallization. In aggregate, large-scale experimental studies support the premise that protein surface properties, especially the prevalence of well-ordered epitopes capable of mediating inter-protein packing interactions, are paramount in determining crystallization propensity. This basis provided the impetus to systematically characterize such epitopes in the existing PDB with the goal of developing methods to use historically successful epitopes for rational engineering of improved protein crystallization.

Hydrodynamic Heterogeneity and Aggregation Impede Crystallization

The final crystallization stock of every protein in the experimental dataset was characterized using gel-filtration/static-light-scattering analyses. Consistent with previous theoretical and protein-engineering studies, stable oligomers crystallize significantly better than monomers. However, hydrodynamic heterogeneity impedes crystallization and aggregation strongly inhibits it. Although formation of specific oligomers strongly promotes crystallization, heterogeneous self-association inhibits it. Successful crystallization thus requires minimal non-specific self-association in dilute aqueous buffers but strong self-association under the low water-activity conditions used to form protein crystals. Accordingly, proteins with crystal structures deposited in the PDB should be enriched for surface epitopes with this special combination of physical properties.

Single Amino-Acid Properties that Promote Crystallization Reduce Protein Solubility

In a follow-up study, equivalent datamining methods were used to analyze correlations between sequence properties and in vivo expression/solubility results (Price et al., 2011, Microbial Informatics and Experimentation, 1:6, doi:10.1186/2042-5783-1-6). This study examined 7733 proteins expressed and purified consistently using a T7 vector in codon-enhanced E. coli BL21λ (DE3) cells (PCT/US11/24251, filed Feb. 9, 2011). The relationship between primary sequence properties and the probability of obtaining a protein preparation useful for structural studies were analyzed. A computational predictor of protein expression/solubility (P_(ES)) was produced (available online at http://nmr.cabm.rutgers.edu:8080/PES/). With the exception of predicted backbone disorder, which inhibits both crystallization and solubility, every sequence property that promotes crystallization reduces solubility and vice-versa. These results demonstrate that single-residue mutations designed to enhance crystallization will tend to reduce the probability of obtaining a soluble protein preparation suitable for crystallization screening (FIG. 7).

Moreover, published results showed that hydrodynamic heterogeneity and aggregation, which are correlated with low solubility, significantly impede crystallization (Price et al., Understanding the physical properties that control protein crystallization by analysis of large-scale experimental data. Nat Biotechnol 27 (1), 51-7 (2009); Ferre-D'Amare and Burley, Use of dynamic light scattering to assess crystallizability of macromolecules and macromolecular assemblies. Structure, 2 (5), 357-9 (1994)). Therefore, any strategy focused on single-residue substitutions will suffer from problems with protein solubility, as observed for the Surface Entropy Reduction method.

Observations on the statistical influence of individual amino acids suggest that more complex sequence epitopes are needed to provide the simultaneous combination of good solubility and low surface entropy characteristic of proteins yielding crystal structures. These observations support the strategy of mining such epitopes out of existing crystal structures in the PDB.

Identification and Analysis of Epitopes Mediating Inter-Protein Packing Interactions in the PDB

A hierarchical analytical scheme was developed to identify contiguous epitopes potentially useful for protein engineering and was used to analyze all inter-protein crystal-packing interactions in the PDB (FIG. 3). Bold lines represent protein chains, grey lines inter-atomic contacts ≤4 Å, and numbered circles show representative elements.

FIGS. 5A-5D show selected statistics from application of our analytical scheme to all crystal structures in the PDB that do not have excessively close inter-protein contacts (39,208 entries). FIG. 5A shows histograms showing distributions of the fraction of residues participating in inter-protein packing contacts. FIG. 5B shows histograms showing number of interfaces per crystal. FIG. 5C is a cumulative distribution graph showing fraction of interfaces equal to or smaller in size than the number indicated on the abscissa. In this graph, residues from the two interacting molecules are counted separately. The curve labeled “Largest” shows data for the single largest non-proper interface in each crystal. FIG. 5D shows cumulative size and range distributions for hierarchically defined packing elements (counting residues from one of the interacting molecules).

The average numbers of total, proper, and non-proper interfaces per protein molecule are 6.9, 1.8 and 5.1, respectively (FIG. 5A). While at least four interfaces are required for a molecule to form a 3-dimensional lattice, fewer are possible if multiple molecules are present in the asymmetric unit. Proteins generally contain only a small number of interfaces above the minimum required for lattice formation, indicating that most interfaces contribute to structural stabilization of the lattice. On average, 50% of surface-exposed residues and 36% of all residues participate in inter-protein packing interactions (FIG. 5B). While interfaces range widely in size, 36% of all interfaces and 42% of non-proper interfaces contain 10 or fewer residues, counting contributions from both sides of the interface (˜5 from each participating molecule) (FIG. 5C). The small size of the average interface is encouraging relative to the feasibility of engineering interface formation. FIG. 5D shows the cumulative size/range distributions for all EBIEs, CBIEs, and half-interfaces (i.e., participating residues from one of the two interacting molecules). These data show that, even though some interfaces are complex, most are topologically simple and local in primary sequence. Half of all half-interfaces are under eight residues in size, and a quarter (8678 total) are under eight residues in range (separation) in the polypeptide chain. FBIEs contain on average fewer than two EBIEs (not shown), and most EBIEs are less than 4 residues in size and 10 in range. These small EBIEs represent prime candidates for engineering improved crystallization.

Quantifying Similarity in the Crystal-Packing Interactions of Homologous Proteins Demonstrates Pervasive Polymorphism in Inter-Protein Interfaces

A general method has been developed to quantify the similarity between different inter-protein packing interfaces formed by homologous proteins. Its foundation is a B-factor-weighted count (C_(ij)) of inter-atomic contacts between residues i and j across the interface:

$C_{ij} = {\sum\limits_{{atom}.{pairs}}\left( \frac{< B >_{2 - {10\%}}}{\sqrt{B_{m}B_{n}}} \right)^{n}}$

The terms B_(m) and B_(n) are the atomic B-factors of the contacting atoms in residues i and j, respectively (i.e., atoms with centers separated by less than 4 Å), while <B>_(2-10%) represents an estimate of the B-factor of the most ordered atoms in the structure (which is calculated as the average B-factor of atoms in the 2^(nd) through 10^(th) percentiles). An upper limit of 1.0 is imposed on the B-factor ratio (i.e., it is set to 1.0 whenever (B_(m)B_(n))^(1/2)<<B>_(2-10%)). The exponent n is an adjustable parameter in our software that allows analyses to be performed either without (n=0) or with (n≥1) down-weighting of contacts between atoms with high B-factors. Such atoms, which have enhanced disorder, may contribute less to interface stabilization, but prior literature on this topic is lacking. Therefore, an analytical approach has been developed facilitating exploration of B-factor effects. Specifically, using higher values of n in our scoring function progressively down-weights high B-factor contacts.

Identification of Statistically Over-Represented Epitope Subsequences in Crystal-Packing Interfaces in the PDB Leads to Novel Ideas for Engineering Improved Protein Crystallization

To identify promising motifs for use in enhancing crystallization propensity, statistical analyses of sequence patterns occurring in protein segments with specific secondary structures were conducted, as analyzed using the DSSP algorithm (Kabsch and Sander, Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22 (12), 2577-637(1983)), which makes three-state assignments of α-helix (H), β-strand (E), or loop or coil (C).

The primary reason for using a simultaneous sequence/secondary-structure definition of a packing epitope is to facilitate application of these data to epitope-engineering. A given amino acid sequence will generally have different conformations at different sites in a protein. However, local conformation is likely to be similar when the sequence occurs in the same secondary structure (i.e., on the surface of a β-strand or in an α-helix capping motif). An epitope-visualization tool, implemented as part of our epitope-engineering web-server described below, enables users to verify this assumption for specific epitopes and provides support for its general validity.

Previously, sophisticated primary-sequence-analysis algorithms have been developed to predict local protein secondary structure as well as surface-exposure even in the absence of the 3-dimensional structure of the protein. PHD-PROF is one such program that was trained using DSSP, the software used to classify all crystal-packing epitopes in the PDB. Productive use was made of PHD-PROF in our published crystallization-datamining studies described above. PHD-PROF has been cross-validated and achieves ˜80% accuracy in identifying residue secondary structure and surface-exposure status based on primary sequence alone. These results support the likely efficacy of using PHD-PROF to predict local secondary structure to guide introduction of historically successful crystallization epitopes at productive sites in proteins with unknown tertiary structure.

The initial approach to prioritizing the most promising crystallization epitope subsequences for engineering applications involves ranking their degree of over-representation in packing contacts in non-BioMT interfaces in the PDB (FIG. 1). Accurate assessment of over-representation requires careful correction for redundancy in previous observations of crystal-packing as well as normalization for the biased distribution of amino acids found on protein surfaces. PSS, described above, is used to quantitatively correct epitope subsequence counts for redundancies between the different packing interfaces in which they are found. The marginal count for each occurrence of a sub-epitope in an interface in a crystal is inversely proportional to the total number of crystals mostly identical to the given crystal, and to the number of interfaces within the crystal mostly identical to the given interface. Epitope subsequences in bio-oligomer (BIOMT) interfaces do not contribute to the count. This approach substantially boosts signal strength by counting the multiple contacts formed by an efficacious epitope subsequence found in crystal structures of homologous proteins when that epitope subsequence repeatedly participates in novel packing interactions.

To calculate the whether a given epitope subsequence appears in crystal packing interfaces more frequently than expected by chance, each epitope subsequences' count must be calibrated against the total number of occurrences of that subsequence in the sequence space of the PDB, and against the variable probability of finding any given amino acid or amino acid sequence on the protein's surface rather than in the interior. For an epitope subsequence with interaction mask m (such as XX or XxxxX), primary and secondary sequence i (such as “ExxxR HhhhH”) and surface exposure profile s (such as SIIIS), its redundancy-weighted count in crystal packing interfaces is e_msi (the “epitope subsequence” count) and its redundancy-weighted count in the sequence space is p_msi (the “prior” count). The surface profile is calculated by DSSP, which uses a quantitative cut-off for designation of interior residues, allowing up to 15% of their surface area to be solvent exposed. Because of this uncertainty, about 10% of all residues participating in packing contacts are designated as interior. Since the surface profile designations are variable and to some degree arbitrary, they need to be abstracted away using the “surface-expected” method, which predicts how frequently a epitope subsequence would participate in crystal packing interactions if the surface profile bias was removed. The total number of occurrences of a epitope subsequence with interaction mask m and sequence i in interactions is the sum of the counts across all possible surface profiles:

e_mi=Σ_s e_msi

While the prior count of a epitope subsequence with mask m and sequence i is accordingly:

p_mi=Σ_s p_msi

The expected number of occurrences of the given epitope subsequence in interactions depends on the frequency of occurrences of all epitope subsequences with the same interaction mask and surface profile, summed across all possible surface profiles:

E(e_mi)=Σ_i[(Σ_j e_msj)/(Σ_j p_msj)*p_msi]

Finally, the probability that the calculated epitope subsequence count could have been observed by chance can be calculated by integrating the upper tail of the binomial distribution B(n, p, k) where:

k_mi=e_mi,

n_mi=p_mi, and

p_mi=E(e_mi)/p_mi.

If the calculated probability is below the Bonferonni-corrected significance level of 5%, the given epitope subsequence is designated to be “over-represented”, and its over-representation ratio is equal to:

e_mi/E(e_mi).

The initial analysis conducted using these methods evaluated all possible secondary-structure-specific epitopes subsequences in protein segments from two to six residues in length. The interacting residues in the epitope subsequence had to occur in a single EBIE, while both the interacting and non-interacting residues had to match the secondary-structure pattern at every position. This analysis covers 31 different interaction masks giving a total of over 57 billion possible secondary-structure-specific sub-epitopes. However, only 54,317,358 of these actually occur in crystal structures in the PDB, so this number was used as the correction factor for multiple-hypothesis testing. After applying this correction, 2,040 of these secondary-structure-specific epitope subsequences are over-represented at a Bonferroni-corrected 5% significance level of 9.2×10⁻¹⁰, while also meeting a small set of additional selection criteria (at least 10 redundancy-corrected counts in epitopes, no more than 50% of occurrences involving non-water bridging solvent species, and at least a 1.5 ratio of redundancy-corrected observed vs. expected counts in epitopes).

Table 37 shows the eight top-ranked secondary-structure-specific epitope subsequences in two classes of interest, continuous dimers (XX mask) and dimers separated by four residues (XxxxX mask).

TABLE 37^(a) Redundancy- Non- Over- % identity in Secondary corrected homologo representation Fraction in Fraction non- partner Sequence structure counts us chains P-value ratio epitopes H₂O solvent epitopes LP CC 3645 2421 5.0e−79  1.3 0.18 0.18 12% GY CC 1961 1241 1.6e−67  1.4 0.22 0.24 12% PN CC 2685 1612 3.9e−62  1.3 0.27 0.19 13% GK CH 497 277 1.7e−61  2.0 0.24 0.74 12% DG CC 5443 2805 7.2e−58  1.2 0.25 0.16 13% PG CC 5008 2600 1.3e−57  1.2 0.25 0.17 12% GF CC 1763 1216 1.0e−55  1.4 0.19 0.21 12% NG CC 4062 2226 2.7e−54  1.2 0.25 0.18 12% ExxxR HhhhH 3547 2041 0.0 2.1 0.28 0.18 15% RxxxE HhhhH 2928 2328 0.0 2.2 0.26 0.17 15% QxxxD HhhhH 1522 1141 1.3e−272 2.3 0.27 0.13 13% RxxxR HhhhH 1627 1078 1.1e−271 2.2 0.28 0.23 15% ExxxE HhhhH 2968 1998 1.6e−251 1.8 0.23 0.16 15% DxxxR HhhhH 1593 1128 4.1e−246 2.2 0.26 0.17 14% ExxxQ HhhhH 1904 1395 3.0e−228 2.0 0.24 0.16 14% AxxxR HhhhH 1717 1299 3.6e−186 1.9 0.17 0.19 14% ^(a)“Sequence” is the string of amino acid letter codes, with capital letters indicating amino acid participating in interactions, and lower-case x's indicating intervening residues (which may or may not be interacting as well). “Secondary structure” indicates structure letter codes (H = helix, E = sheet, C = coil). “Redundancy-corrected counts” is calculated as described in above. “Non-homologous chains” is the number of chain homology sets in which the epitope can be found in interactions (a chain homology set contains all protein chains that have greater than 25% sequence identity). “P-value” and “over-representation ratio” are calculated as described above. “Fraction in epitopes” is the ratio of the observed redundancy-weighted surface-profile-summed epitope count to the observed prior count. “Fraction non-water solvent” is the fraction of the total redundancy-weighted number of occurrences of the epitope that participate in inter-protein interactions bridged by a solvent molecule other than water, such as salt ions or nucleotides (ATP). “% id partner epitopes” is the average sequence identity of the partner epitopes of this epitope—the strings of amino acid letter codes corresponding to the residues of the protein with which the residues of the given epitope interact in every interface in which the epitope appears.

Evaluation of these classes is informative for several reasons, including the fact their P-values can be compared directly because they have an equivalent number of occurrences in the PDB. The most over-represented epitope subsequences in the two classes contain different residues, indicating that our statistical methods give results sensitive to local stereochemistry and not merely the amino acid composition. The top-ranking continuous dimers are enriched in Gly residues in loops, consistent with prediction from our earlier crystallization datamining studies that such residues are enriched in packing interfaces (Price et al., Understanding the physical properties that control protein crystallization by analysis of large-scale experimental data. Nat Biotechnol 27 (1), 51-7 (2009)).

Remarkably, dimers separated by four residues are enriched in high-entropy, charged amino acids located on the surfaces of α-helices or in their capping motifs. Given these relative locations, the high-entropy side-chains are likely to be entropically restricted by mutual salt-bridging or hydrogen-bonding (H-bonding) interactions within the secondary-structure specific epitope subsequence. Immobilization of these high-entropy side-chains by local tertiary interactions in the native structure of a protein enables them to participate in crystal-packing interactions without incurring the entropic penalty associated with their immobilization from a disordered conformation on the surface of the protein.

Simple Local Structural Motifs Represent Highly Promising Candidates for Engineering Improved Protein Crystallization Behavior Based on Novel Amino-Acid Substitutions

Certain local structural motifs are highly polar and therefore much less likely than hydrophobic substitutions to reduce protein solubility, which is a major problem with the Surface Entropy Reduction method (Cooper et al., Protein crystallization by surface entropy reduction: optimization of the SER strategy. Acta crystallographica, 63 (Pt 5), 636-45 (2007); Derewenda and Vekilov, Entropy and surface engineering in protein crystallization. Acta crystallographica 62 (Pt 1), 116-24 (2006); Longenecker et al., Protein crystallization by rational mutagenesis of surface residues: Lys to Ala mutations promote crystallization of RhoGDI. Acta crystallographica, 57 (Pt 5), 679-88 (2001)). Second, they occur in secondary-structure motifs that are reliably classified by standard prediction algorithms, both in terms of their location and their solvent exposure status. Therefore, epitope-engineering efforts should be able to efficiently target the most promising regions of the subject protein, even when its tertiary structure is unknown. Third, it is reassuring that the sub-epitopes in both classes in Table 37 interact with partner epitopes with highly diverse sequences, consistent with our goal of engineering the surface of a protein to have higher interaction probability (i.e., rather than attempting to engineer specific pair-wise packing interactions). Table 38 only shows a small fraction of the statistically over-represented secondary-structure-specific sub-epitopes in the PDB. The full set in Table 37 (Appendix A) covers a much wider variety of sequences and secondary structures, although many of them echo similar physiochemical themes.

Epitope-Engineering Software

Software was written to determine all possible ways that the statistically over-represented epitope subsequences described above can be introduced into a target protein consistent with the sequence profile of the corresponding functional family (FIG. 1). The program takes two input files, one a FASTA-formatted file with a set of homologous protein sequences (with the target protein at the top) and the other the secondary-structure prediction output from PHD/PROF. After using ClustalW to align the homologs, the software systematically analyzes the locations where any of the sub-epitopes can be engineered into the target protein consistent with two criteria.

First, based on the PHD/PROF prediction, the secondary structure at the site of mutagenesis must be likely to match that of the sub-epitope. This restriction increases the probability that the engineered sub-epitope will have a local tertiary structure similar to the over-represented sub-epitopes in the PDB.

Second, in one embodiment, the engineered epitope subsequence contains exclusively amino acids observed to occur at the equivalent position in one of the homologs. In another embodiment, the engineered epitope subsequence is filtered to not contain residues anti-correlated in homologs with other amino acids in the target sequence, as determined using the “correlated evolution” metrics described above. Restricting epitope mutations to substitutions observed in a homolog should reduce the chance that the mutations will impair protein stability. In yet another embodiment, the engineered epitope subsequence is not restricted at all based on homolog sequence, and a greater risk of protein destabilization is tolerated. The computer program returns a comma-separated-value file containing a list of candidate epitope-engineering mutations along with statistics characterizing each epitope subsequence. While this list is sorted according to over-representation P-value, it is readily resorted according to user criteria in any standard spreadsheet program. For a target protein ˜200 residues in length with ˜20 homologous sequences, the program typically returns several hundred candidate mutations. However, longer proteins or proteins with more homologs can yield lists containing thousands of candidate mutations.

Methods for Protein Expression

Strategies and techniques for expressing a protein of interest or a modified protein, for producing nucleic acids encoding a protein of interest or a modified protein are well-known in the art and can be found, e.g., in Berger and Kimmel, Guide to Molecular Cloning Techniques, Methods In Enzymology Vol. 152 Academic Press, Inc., San Diego, Calif. and in Sambrook et al., Molecular Cloning—A Laboratory Manual (2nd ed.) Vol. 1-3 (1989) and in Current Protocols In Molecular Biology, Ausubel, F. M., et al., eds., Greene Publishing Associates, Inc. and John Wiley & Sons, Inc., (1996 Supplement).

Expression systems suitable for use with the methods described herein include, but are not limited to in vitro expression systems and in vivo expression systems. Exemplary in vitro expression systems include, but are not limited to, cell-free transcription/translation systems (e.g., ribosome based protein expression systems). Several such systems are known in the art (see, for example, Tymms (1995) In vitro Transcription and Translation Protocols: Methods in Molecular Biology Volume 37, Garland Publishing, NY).

Exemplary in vivo expression systems include, but are not limited to prokaryotic expression systems such as bacteria (e.g., E. coli and B. subtilis), and eukaryotic expression systems including yeast expression systems (e.g., Saccharomyces cerevisiae), worm expression systems (e.g. Caenorhabditis elegans), insect expression systems (e.g. Sf9 cells), plant expression systems, amphibian expression systems (e.g. melanophore cells), vertebrate including human tissue culture cells, and genetically engineered or virally infected whole animals.

Methods Fore Determining Solubility of a Protein

Methods for determining the solubility of a protein are known in the art.

For example, a recombinant protein can be isolated from a host cell by expressing the recombinant protein in the cell and releasing the polypeptide from within the cell by any method known in the art, including, but not limited to lysis by homogenization, sonication, French press, microfluidizer, or the like, or by using chemical methods such as treatment of the cells with EDTA and a detergent (see Falconer et al., Biotechnol. Bioengin. 53:453-458 [1997]). Bacterial cell lysis can also be obtained with the use of bacteriophage polypeptides having lytic activity (Crabtree and Cronan, J. E., J. Bact., 1984, 158:354-356).

Soluble materials can be separated form insoluble materials by centrifugation of cell lysates (e.g. 18,000×G for about 20 minutes). After separation of lysed materials into soluble and insoluble fractions, soluble protein can be visualized by using denaturing gel electrophoresis. For example, equivalent amount of the soluble and insoluble fractions can be migrated through the gel. Proteins in both fractions can then be detected by any method known in the art, including, but not limited to staining or by Western blotting using an antibody or any reagent that recognizes the recombinant protein.

Protein Purification

Proteins can also be isolated from cellular lysates (e.g. prokaryotic cell lysates or eukaryotic cell lysates) by using any standard technique known in the art. For example, recombinant polypeptides can be engineered to comprise an epitope tag such as a Hexahistidine (“hexaHis”) tag or other small peptide tag such as myc or FLAG. Purification can be achieved by immunoprecipitation using antibodies specific to the recombinant peptide (or any epitope tag comprised in the amino sequence of the recombinant polypeptide) or by running the lysate solution through an affinity column that comprises a matrix for the polypeptide or for any epitope tag comprised in the recombinant protein (see for example, Ausubel et al., eds., Current Protocols in Molecular Biology, Section 10.11.8, John Wiley & Sons, New York [1993]).

Other methods for purifying a recombinant protein include, but are not limited to ion exchange chromatography, hydroxylapatite chromatography, hydrophobic interaction chromatography, preparative isoelectric focusing chromatography, molecular sieve chromatography, HPLC, native gel electrophoresis in combination with gel elution, affinity chromatography, and preparative isoelectric. See, for example, Marston et al. (Meth. Enz., 182:264-275 [1990]).

Screening of Modified Proteins for Crystallization

Initial high-throughput crystallization screening can be conducted using methods known in the art, for example manually or using the 1,536-well microbatch robotic screen at the Hauptmann-Woodward Institute (Cumbaa et al., Automatic classification of sub-microlitre protein-crystallization trials in 1536-well plates. Acta Crystallogr. 59, 1619-1627 (2003)). Proteins failing to yield rapidly progressing crystal leads can be subjected to vapor diffusion screening, typically 300-500 conditions (e.g., Crystal Screens I & II, PEG-Ion and Index screens from Hampton Research or equivalent screens from Qiagen) at either 4° C., 20° C. or both. Screening can be conducted in the presence of substrate or product compounds if commercially available. Screening can also be conducted using the target protein as a control to evaluate the effect of the introduction of an epitope or multiple epitopes on the crystallization properties of the target protein.

All patents, patent applications and publications cited herein are hereby incorporated by reference in their entirety. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described herein.

The following examples illustrate the present invention, and are set forth to aid in the understanding of the invention, and should not be construed to limit in any way the scope of the invention as defined in the claims which follow thereafter.

EXAMPLES

This invention is further illustrated by the following examples, which should not be construed as limiting. Those skilled in the art will recognize, or be able to ascertain, using no more than routine experimentation, numerous equivalents to the specific substances and procedures described herein. Such equivalents are intended to be encompassed in the scope of the claims that follow the examples below.

Example 1

Introduction of Residues from an Observed Crystal-Packing Epitope Improves Crystallization of an Integral Membrane Protein

FIGS. 8A-8C show representative results from an initial attempt to employ a previously observed crystallization epitope to improve the crystallization of a difficult protein. FIG. 8A is a schematic summary of the results from a representative initial crystallization screen at 20° C. The MD-to-AG mutant yielded 5 excellent hits and 23 total hits, compared to 1 and 8, respectively, for the wild-type protein. FIG. 8B is a micrograph of one well of excellent lead crystals obtained for the MD-to-AG mutant protein (described below) in this screen. FIG. 8C is the same well from a wild-type screen conducted in parallel.

The subject of this study was a polytopic integral membrane protein from E. coli called B0914 whose wild-type sequence only yields poor crystals. Manual inspection of a crystal structure of a remote homologue (Dawson and Locher, Structure of a bacterial multidrug ABC transporter. Nature 443 (7108), 180-5 (2006)) revealed that an Ala-Gly (AG) dipeptide in a periplasmic loop formed part of a crystal-packing interaction. Because the frequency of these two residues correlates most strongly with successful crystal structure determination in our published datamining studies, it was hypothesized that this dipeptide could be used to engineer improved crystallization of another protein. This sub-epitope ranks 20^(th) among the 400 possibilities in the analysis of over-represented continuous dimers.

The sub-epitope was introduced into one of the periplasmic loops in protein B0914, at a site with the sequence met-asp (MD) but where the sequence AG is found in a homolog. This MD-to-AG mutant protein yields more hits and more high quality hits in initial crystallization screens (FIGS. 8A-8C). Importantly, improved crystallization is obtained even though the interaction partner of the AG epitope from the existing structure was not introduced into the target protein. A second mutant protein containing a similarly chosen crystallization epitope that was not observed in a homologous protein failed to produce properly folded protein, while a series of single-residue substitutions chosen based on different criteria yielded inferior results, including several substitutions recommended by the standard Surface Entropy Reduction algorithm.

Example 2

Generation of Modified Proteins with Epitopes that Increase Protein Crystallization

Amino acid sequences of 13 genes were provided to the server. The amino acid sequences were:

BhR182-21.1 (SEQ ID NO: 1) MIIREATVQDYEEVARLHTQVHEAHVKERGDIFRSNEPTLNPSFFQAAVQ GEKSTVLVFVDEREKIGAYSVIHLVQTPLLPTMQQRKTVYISDLCVDETR RGGGIGRLIFEAIISYGKAHQVDAIELDVYDFNDRAKAFYHSLGMRCQKQ TMELPLLEHHHHHH ChR11B-227-489-21.2 (SEQ ID NO: 2) NDDVEFRYADFLFKNNNYAEAIEVFNKLEAKKYNSPYIYNRRAVCYYELA KYDLAQKDIETYFSKVNATKAKSADFEYYGKILMKKGQDSLAIQQYQAAV DRDTTRLDMYGQIGSYFYNKGNFPLAIQYMSKQIRPTTTDPKVFYELGQA YYYNKEYVKADSSFVKVLELKPNIYIGYLWRARANAAQDPDTKQGLAKPY YEKLIEVCAPGGAKYKDELIEANEYIAYYYTINRDKVKADAAWKNILALD PTNKKAIDGLKMKLEHHHHHH CvR75A-1-152-21.17 (SEQ ID NO: 3) MKKVYIKTFGCQMNEYDSDKMADVLGSAEGMVKTDNPEEADVILFNTCSV REKAQEKVFSDLGRIRPLKEANPDLIIGVGGCVASQEGDAIVKRAPFVDV VFGPQTLHRLPDLIESRKQSGRSQVDISFPEIEKFDHIPPAKVDGGAAFV SILEHHHHHH EcoxPrrC (SEQ ID NO: 4) MGKTLSEIAQQLSTPQKVKKTVHKEVEATRAVPKVQLIYAFNGTGKTRLS RDFKQLLESKVHDGEGEDEAEQSALSRKKILYYNAFTEDLFYWDNDLQED AEPKLKVQPNSYTNWLLTLLKDLGQDSNIVRYFQRYANDKLTPHFNPDFT EITFSMERGNDERSAHIKLSKGEESNFIWSVFYTLLDQVVTILNVADPDA RETHAFDQLKYVFIDDPVSSLDDNHLIELAVNLAGLIKSSESDLKFIITT HSPIFYNVLFNELNGKVCYMLESFEDGTFALTEKYGDSNKSFSYHLHLKQ TIEQAIADNNVERYHFTLLRNLYEKTASFLGYPKWSELLPDDKQLYLSRI INFTSaSTLSNEAVAEPTPAEKATVKLLLDHLKNNCGFWQQEQKNG ER247A-21.2 (SEQ ID NO: 5) MNETAVYGSDENIIFMRYVEKLHLDKYSVKNTVKTETMAIQLAEIYVRYR YGERIAEEEKPYLITELPDSWVVEGAKLPYEVAGGVFIIEINKKNGCVLN FLHSKLEHHHHHH ER40-21-mgk (SEQ ID NO: 6) MSDDNSHSSDTISNKKGFFSLLLSQLFHGEPKNRDELLALIRDSGQNDLI DEDTRDMLEGVMDIADQRVRDIMIPRSQMITLKRNQTLDECLDVIIESAH SRFPVISEDKDHIEGILMAKDLLPFMRSDAEAFSMDKVLRQAVVVPESKR VDRMLKEFRSQRYHMAIVIDEFGGVSGLVTIEDILELIVGEIEDEYDEED DIDFRQLSRHTWTVRALASIEDFNEAFGTHFSDEEVDTIGGLVMQAFGHL PARGETIDIDGYQFKVAMADSRRIIQVHVKIPDDSPQPKLDELEHHHHHH EwR161-21.1 (SEQ ID NO: 7) MQSFDVVIAGGGMVGLALACGLQGSGLRIAVLEKQAAEPQTLGKGHALRV SAINAASECLLRHIGVWENLVAQRVSPYNDMQVWDKDSFGKISFSGEEFG FSHLGHIIENPVIQQVLWQRASQLSDITLLSPTSLKQVAWGENEAFITLQ DDSMLTARLVVGADGAHSWLRQHADIPLTFWDYGHHALVANIRTEHPHQS VARQAFHGDGILAFLPLDDPHLCSIVWSLSPEQALVMQSLPVEEFNRQVA MAFDMRLGLCELESERQTFPLMGRYARSFAAHRLVLVGDAAHTIHPLAGQ GVNLGFMDVAELIAELKRLQTQGKDIGQHLYLRRYERRRKHSAAVMLASM QGFRELFDGDNPAKKLLRDVGLVLADKLPGIKPTLVRQAMGLHDLPDWLS AGKLEHHHHHH HR4403-86-543-14.1 (SEQ ID NO: 8) MGHHEIHRHSHMNRFEEAKRTYEEGLKHEANNPQLKEGLQNMEARLAERK FMNPFNMPNLYQKLESDPRTRTLLSDPTYRELIEQLRNKPSDLGTKLQDP RIMTTLSVLLGVDLGSMDEEEEIATPPPPPPPKKETKPEPMEEDLPENKK QALKEKELGNDAYKKKDFDTALKHYDKAKELDPTNMTYITNQAAVYFEKG DYNKCRELCEKAIEVGRENREDYRQIAKAYARIGNSYFKEEKYKDAIHFY NKSLAEHRTPDVLKKCQQAEKILKEQERLAYINPDLALEEKNKGNECFQK GDYPQAMKHYTEAIKRNPKDAKLYSNRAACYTKLLEFQLALKDCEECIQL EPTFIKGYTRKAAALEAMKDYTKAMDVYQKALDLDSSCKEAADGYQRCMM AQYNRHDSPEDVKRRAMADPEVQQIMSDPAMRLILEQMQKDPQALSEHLK NPVIAQKIQKLMDVGLIAIR KR127C-21.3 (SEQ ID NO: 9) IDNPTPKSSMTFKELYDEWLLVYEKEVQNSTYYKTTRAFEKHVLPVIGST KLSDFTPMELQNFRNDLSEKLKFARKLFGMVRKVFNHAALLSYIQANPAL PVTSQGIKLEHHHHHH MaR262-21.1 (SEQ ID NO: 10) MPESYWEKVSGKNIPSSLDLYPIIHNYLQEDDEILDIGCGSGKISLELAS LGYSVTGIDINSEAIRLAETAARSPGLNQKTGGKAEFKVENASSLSFHDS SFDFAVMQAFLTSVPDPKERSRIIKEVFRVLKPGAYLYLVEFGQNWHLKL YRKRYLHDFPITKEEGSFLARDPETGETEFIAHHFTEKELVFLLTDCRFE IDYFRVKELETRTGNKILGFVIIAQKLLEHHHHHHIMRFYGADDAIQSGE YQMPEIKVVK PaeKu (SEQ ID NO: 11) MARAIWKGAISFGLVHIPVSLSAATSSQGIDFDWLDQRSMEPVGYKRVNK VTGKEIERENIVKGVEYEKGRYVVLSEEEIRAAHPKSTQTIEIFAFVDSQ EIPLQHFDTPYYLVPDRRGGKVYALLRETLERTGKVALANVVLHTRQHLA LLRPLQDALVLITLRWPSQVRSLDGLELDESVTEAKLDKRELEMAKRLVE DMASHWEPDEYKDSFSDKIMKLVEEKAAKGQLHAVEEEEEVAGKGADIID

Each target sequence was then entered into the protein crystallization server, along with a PROF secondary structure prediction and a FASTA file containing about 50 homologous protein sequences for each target.

Criteria used to select the epitope subsequences expected to improve crystallizability of the proteins included: (1) prioritization by overrepresentation ratio, using P-value cutoff; (2) prioritization of mutations improving over-representation ratio at a given site (i.e., avoiding removing an epitope subsequence with a better ratio than the new epitope subsequence); (3) prioritization of epitope subsequences observed in packing interactions in at least 50 sequence-unrelated proteins (“chainsets” as defined above) in the PDB; and (4) favoring of substitutions maintaining or increasing polarity over those reducing polarity.

The server outputted several hundred possible mutations that introduce one epitope from the epitope library at some position in the protein sequence, with considerations given to primary and secondary structure conservation. The output list was ranked by the over-representation ratio of each candidate epitope.

The researchers went down the list and use their knowledge of the target protein's biophysics and biochemistry to guide their selection of epitopes, skipping epitopes that they believe would endanger the protein's biological activity or structural stability. The researchers decide whether they want to introduce a small and simple or a larger and more complex epitope, and whether the suggested epitope mutation is better than any existing epitope it replaces. In addition to these constraints, the researchers use the epitopes' over-representation ratios, P-values, in-epitopes fractions, non-homologous chainset counts, and non-water solvent fractions to decide which epitopes are better for the given situation. The researchers are able to pick a few, several, or many mutations from the candidates list to engineer in parallel, depending on the available resources and the degree of importance of obtaining a structure.

Some of the engineered proteins and the recommended epitopes chosen for protein expression and crystallization studies are shown in Table 38.

TABLE 38 Sequence Original ID Number Gene Position Sequence Sub-epitope* 42 BhR182 11 YEEVA YxxxN/HHHHH 43 BhR182 134 DRAKA ExxxR/HHHHH 44 BhR182 39 TLNPSF TxxxxR/CCHHHH 45 BhR182 12 EEVAR YxxxR/HHHHH 46 BhR182 97 DETRRG DxxGxG/CCCCCC 2 CvR75A 90 AIVKR ExxxR/HHHHH 13 CvR75A 19 DKMAD ExxxR/HHHHH 14 CvR75A 65 IRPLK YxxxQ/HHHHH 15 CvR75A 64 RIRP RxxE/HHHH 3 ER40 93 KxxxE 20 ER40 19 FSLLL FxxxQ/HHHHH 21 ER40 38 LALIR ExxxR/HHHHH 22 ER40 245 QAFG SAxG/HHHC 1 HR4403 354 IKGYT ISxxT/CCHHH 4 KR127C 106 YKTEN 27 KR127C 76 KLFGM YxxxM/HHHHH 28 KR127C 55 FTPME LTxxE/CCHHH 29 KR127C 101 PVTSQG DxxGxG/CCCCCC 7 MaR262 38 GCGSG ACxxG 8 MaR262 129 RVLKPG RxxxPE 9 MaR262 48 LASLGY LxxKxY 18 MaR262 188 KELVF KxxxE 6 SiR159 90 RMRAR RxxxH/HHHHH 38 SiR159 44 KSLG SxxG/ECCE 39 SiR159 340 ARCG RxxG/HHCC 40 SiR159 32 SQDAG SxxxH/HHHHH 41 SiR159 140 ADAPVQ LxxxxQ/CCHHHH 5 VpR106 233 KQWLD QxxxD/HHHHH 16 VpR106 57 PLNRFQ LxxxxQ/CCHHHH 17 VpR106 60 RFQNI ExxxR/HHHHH 19 VpR106 42 EAYKF ExxxR/HHHHH *Includes secondary structure class: H = helix, E = β-strand and C is coil.

Example 3 Protein Expression and Crystallization Screening

Proteins from Example 2 are expressed, purified, concentrated to 5-12 mg/ml, and flash-frozen in small aliquots as described in Acton et al., Robotic cloning and Protein Production Platform of the Northeast Structural Genomics Consortium. Methods in Enzymology 394, 210-243 (2005). All proteins contain short 8-residue hexa-histidine purification tags at their N- or C-termini and are metabolically labeled with selenomethionine. Matrix-assisted laser-desorption mass spectrometry is used to verify construct molecular weight. All proteins are ≥95% pure based on visual inspection of Coomasie Blue stained SDS-PAGE gels. The distribution of hydrodynamic species in the protein stock is assayed using static light-scattering and refractive index detectors (Wyatt, Inc., Santa Barbara, Calif.) to monitor the effluent from analytical gel filtration chromatography in 100 mM NaCl, 0.025% (w/v) NaN₃, 100 mM Tris-Cl, pH 7.5, on a Shodex 802.5 column (Showa Denko, Tokyo, Japan). Protein samples are flash frozen in liquid nitrogen in small aliquots prior to crystallization or biophysical characterization. Oligomeric state is inferred from the molecular weight determined by Debye analysis of the light-scattering data (Price et al., Understanding the physical properties that control protein crystallization by analysis of large-scale experimental data. Nat Biotechnol 27 (1), 51-7 (2009)).

Initial high-throughput crystallization screening is conducted using the 1,536-well microbatch robotic screen at the Hauptmann-Woodward Institute (Cumbaa et al., Automatic classification of sub-microlitre protein-crystallization trials in 1536-well plates. Acta Crystallogr. 59, 1619-1627 (2003)). Proteins failing to yield rapidly progressing crystal leads are subjected to vapor diffusion screening, typically 300-500 conditions (Crystal Screens I & II, PEG-Ion and Index screens from Hampton Research or equivalent screens from Qiagen) at both 4° C. and 20° C. Screening is conducted in the presence of substrate or product compounds if commercially available.

Crystal optimization, diffraction data collection at cryogenic temperatures, structure solution using single or multiple-wavelength anomalous diffraction techniques and refinement are conducted using standard methods.

Example 4 Analysis of Intermolecular Packing Interactions in the Protein Data Bank to Guide Rational Engineering of Protein Crystallization.

X-ray crystallography is the dominant method for solving protein structures, but despite decades of methodological improvement, most proteins do not yield solvable crystals. Even when selected using the best algorithms available, at most 60% of proteins give crystals of any kind, and no more than 35% give crystals which can be solved. The reasons for this low success rate remain obscure due to our limited understanding of crystallization itself. A better understanding of crystallization is required to identify both problematic areas of the process and potential solutions to this critical barrier. Working within this framework, and as described herein, is a characterization the stereochemical features of crystal packing interactions to guide rational engineer protein sequences to improve crystallization. Described herein is a rigorous parsing of all protein crystal structures in the Protein Data Bank (PDB) to identify and characterize crystal packing patterns. All residues within a minimum contact distance between chains are identified and then grouped into an ascending hierarchy ranging from the simplest elementary binary interacting epitopes to complete binary interprotein interaction interfaces. For counting and averaging purposes, protein chains are redundancy-downweighted to account for homologous chains forming similar crystals, as evaluated by a dot-product-like Packing Similarity Score. Also described herein is an identification of sequences which appear disproportionately frequently in packing interfaces relative to their background frequency in the PDB. These overrepresented sequences are more efficacious at forming favorable packing interactions, and therefore offer attractive possibilities for new engineering approaches to enhance protein crystallizability.

More than 50 years after the solution of the first protein crystal structure Kendrew, et al., Nature 1958, 181 (4610), 662-6), protein crystallization remains a hit-or-miss proposition. However, as long as most proteins cannot be crystallized, crystallization fundamentally remains a hit-or-miss proposition. Synergistic developments in crystallographic methods, synchrotron beamlines, and high-speed computing have made structure solution and refinement routine, even for very large complexes, as long as high-quality crystals are available. However, there has been comparatively little progress in improving methods for protein crystallization. Recent work by structural genomics (SG) consortia has systematically confirmed that most naturally occurring proteins do not readily yield high-quality crystals suitable for x-ray structure determination and that crystallization is the major obstacle to the determination of protein structures using diffraction methods (Canaves, et al., Journal of molecular biology 2004, 344 (4), 977-91; Slabinski, et al., Protein Sci 2007, 16 (11), 2472-82). Many impressive technological innovations during the last 20 years have simplified and streamlined the work involved in protein crystallization. These include the development of highly efficacious chemical screens that mimic historically successful crystallization conditions (Price, et al., Nat Biotechnol 2009, 27 (1), 51-7), sophisticated robotics that enable more crystallization conditions to be screened with less protein and effort (Cooper, et al., Acta crystallographica 2007, 63 (Pt 5), 636-45; Derewenda, Methods 2004, 34 (3), 354-63), and numerous other clever innovations that improve the crystallization process in some cases. Even with these advances, only approximately ⅓ of proteins with even the most promising sequence properties yield crystal structures from a single protein construct.

Existing methods for engineering improved protein crystallization work with limited efficiency. Consistent with this premise, changes in primary sequence have been demonstrated to substantially alter the crystallization properties of many proteins (Derewenda, Acta crystallographica 2006, 62 (Pt 1), 116-24; Stanley, Science (New York, N.Y 1935, 81 (2113), 644-645). Disordered backbone segments can be identified using elegant hydrogen-deuterium exchange mass spectrometry methods, and genetically engineered constructs with such segments excised have shown improved crystallization properties (Edsall, Journal of the history of biology 1972, 5 (2), 205-57). Progressive truncation of the N- and C-termini of the protein can also yield crystallizable constructs of proteins that initially failed to crystallize (Hunt and Ingram, Nature 1958, 181 (4615), 1062-3). However, many nested truncation constructs generally need to be screened, sometimes with termini differing by as little as two amino acids, and this procedure still frequently fails to yield a soluble protein construct producing high-quality crystals. The Surface Entropy Reduction (SER) method developed by Derewenda and co-workers uses site-directed mutagenesis to replace high-entropy side chains on the surface of the protein (generally lysine, glutamate, and glutamine) with lower entropy side chains (generally alanine) (Derewenda, Acta crystallographica 2006, 62 (Pt 1), 116-24; Stanley, Science (New York, N.Y 1935, 81 (2113), 644-645; Lessin, et al., J Exp Med 1969, 130 (3), 443-66). In most cases in which a substantial improvement in crystallization has been obtained by this method, a pair of such mutations were introduced at adjacent sites. While some spectacular successes have been obtained this way, most such mutations reduce the solubility of the protein, frequently so severely that a high quality protein preparation can no longer be obtained. Most attempts to employ this technique in the Hunt lab have resulted in production of insoluble protein (unpublished results). The Derewenda group has also evaluated the use of amino acids other than alanine to replace high-entropy side chains (Derewenda, Acta crystallographica 2006, 62 (Pt 1), 116-24; Kendrew, et al., Proc R Soc Lond A Math Phys Sci 1948, 194 (1038), 375-98). These substitutions frequently change the crystallization properties of the protein, but so far, there is no report of such alternative substitutions being used to efficiently engineer crystallization of an otherwise crystallization-resistant protein.

Recent large-scale experimental studies have shown that the surface properties of proteins, and particularly the entropy of the exposed side chains, are a major determinant of protein crystallization propensity (Slabinski, et al., Protein Sci 2007, 16 (11), 2472-82). These studies demonstrated that overall thermodynamic stability is not a major determinant of protein crystallization propensity. They also identified a number of primary sequence properties that correlate with crystallization success, including the fractional content of several individual amino acids. Unfortunately, further studies have demonstrated that every individual amino acid that positively correlates with crystallization success negatively correlates with protein solubility, and vice versa. This effect severely limits the efficacy of using single amino acid substitutions to engineer improved protein crystallization because crystallization probability is low unless starting with a monodisperse soluble protein preparation. Moreover, hydrodynamic heterogeneity and aggregation, which are correlated with low solubility, significantly impede crystallization (Slabinski, et al., Protein Sci 2007, 16 (11), 2472-82; Edsall, Journal of the history of biology 1972, 5 (2), 205-57). Therefore, any engineering strategy focused on single-residue substitutions is likely to suffer from problems with protein solubility, as has been observed for the Surface Entropy Reduction method (Stanley, Science (New York, N.Y 1935, 81 (2113), 644-645; Lessin, J Exp Med 1969, 130 (3), 443-66; Ferre-D'Amare, Structure 1994, 2 (5), 357-9). More complex approaches than single amino-acid substitutions are needed for efficient engineering of improved protein crystallization.

Described herein is an analysis of crystal-packing interactions in the Protein Data Bank based on a new analytical framework specifically developed to support rational engineering of improved protein crystallization. Also described herein are results demonstrating such approaches based on introduction of more complex sequence epitopes that have already been observed to mediate high-quality packing contacts in crystal structures deposited into the Protein Data Bank (PDB). Many naturally occurring proteins have excellent solubility properties and also crystallize very well. The results described herein show that specific protein surface epitopes can mediate strong interprotein interactions under the special solution conditions that drive protein crystallization without compromising solubility in the dilute aqueous buffers used for protein purification.

Beyond providing a library of previously observed linear crystal-packing epitopes, this analysis provides new insight into the physiochemical properties of protein crystals. Packing interactions typically involve approximately half of all residues on the protein surface, and are extremely polymorphic among proteins with very high homology, even those with nearly identical cell unit cell constants. However, there are indications that some sequences can preferentially mediate high-quality packing interactions. Furthermore, most isolated packing epitopes are small in size and extent, suggesting that they may be feasible targets for engineering efforts.

Example 5 Identification and Analysis of Sequence Epitopes Mediating Interprotein Packing Interactions in the PDB.

Described herein is a hierarchical analytical scheme to identify contiguous epitopes potentially useful for protein engineering (FIG. 3). This scheme is used to analyze all interprotein packing interactions in crystal structures in the PDB (FIG. 5). The hierarchical scheme is at the heart of our analysis. As used herein, an interface refers to all residues making atomic contacts (≤4 Å) between two protein molecules related by a single rotation-translation operation in the real-space crystal lattice. The interface is decomposed into features that we call Elementary Binary Interaction Epitopes (EBIEs—top of FIG. 3). These comprise a connected set of residues that are covalently bonded or make van der Waals interactions to one other in one molecule and that also contact a similarly connected set of residues in the other molecule forming the interface. EBIEs are the foundation of the analysis described herein because they represent potentially engineerable sequence motifs. One or more EBIEs that are connected to one another by covalent bonds or van der Waals interactions within a molecule form a Continuous Binary Interaction Epitope (CBIE). One or more CBIEs in one molecule that are connected to one another indirectly by a chain of contacts across a single interface form a Full Binary Interaction Epitope (FBIE). The set of one or more FBIEs that all mediate contacts between the same two molecules in the real-space lattice form a complete interface (bottom of FIG. 3).

The results of applying this analytical scheme to the entire PDB are shown in FIGS. 5A-5D. On average, approximately half of all surface-exposed residues participate in crystal packing interactions (FIG. 5B). Protein chains form a plurality of interfaces each, with many more non-proper interfaces than proper interfaces formed (FIG. 5C). The set of proper interfaces, which are more likely to be oligomers or biological interfaces, contains many more larger interfaces than nonproper interfaces (FIG. 5D). However, while these data describe the composition of the crystal structures in the PDB as a whole, they do not address complications raised by nonhomogoneities within the population of the PDB. In particular, two issues need to be addressed. First, FIG. 5B-D shows that proper interfaces behave significantly differently from nonproper interfaces, indicating that they should be segregated for analysis. Second, the PDB contains many structures which are partially or completely redundant, which creates small inaccuracies in the characterization of structures in general but much larger problems in the eventual identification of sequence motifs which are overrepresented in crystal packing interactions. As described herein, both of these concerns are addressed by computational flagging and downweighting mechanisms.

The BioMT database, which categorizes all previously described biological interfaces in the PDB, was used to identify biological oligomers. Interfaces so identified were flagged as “BioMT” interfaces. Recognizing that some potential oligomeric interfaces may not be appropriately categorized by BioMT, the set of “proper” interfaces which could be either biological or crystallographic were also identified.

Interfaces were designated as “proper” if they form part of a regular oligomer with proper rotational symmetry (i.e., n protein molecules in the realspace lattice each related to the next by a 360°/n rotation±5°, with n being any integer from 2-12) and “non-proper” if they do not. Proper interfaces could potentially be part of a stable physiological oligomer while non-proper interfaces cannot. After these two categorization steps, four sets of interfaces exist: the set of all interfaces; the set of biological interfaces identified by BioMT; the set of proper interfaces not identified as biological interfaces by BioMT, but which could potentially be either biological or crystallographic; and the set of interfaces which are not identified by BioMT and which are not proper, as defined above. The most conservative approach to isolating non-physiological crystal packing interactions is to focus exclusively on non-proper interfaces in order to exclude any complex that is potentially a physiological oligomer. Nonetheless, epitopes that contribute to stabilizing physiological oligomers may still be useful for engineering purposes, and epitopes that promote formation of a regular oligomer would be particularly useful because stable oligomerization strongly promotes crystallization (Slabinski, Protein Sci 2007, 16 (11), 2472-82).

Even when all biological and oligomeric interfaces have been removed from the dataset, significant redundancy remains within the PDB. Many proteins in the PDB have had multiple crystal structures deposited, which may have very similar if not identical packing interactions (e.g., multiple mutations at a non-interacting active site) but which can also have completely separate packing interactions (e.g., crystallization under different conditions into a different crystal form). Simply culling identical or homologous proteins would remove all redundancy but would also eliminate significant information from the second situation, where the same protein forms crystals with different packing interactions. To implement a redundancy down-weighting, the Packing Similarity Score (PSS) was developed to evaluate the similarity between interprotein interfaces, full chain interactions, and crystals. PSS is calculated in the following way (more details are included in Methods): Interactions matrices are generated for each interface, with rows representing residues in one chain and columns representing residues in the other chain. Cells in the matrix include the number of interatomic contacts between the two residues (including bonds mediated by a single solvent molecule) and the B-factor-derived weight associated with that contact. The PSS between two interfaces is defined as the Frobenius product (essentially a matrix dot-product) of the two sequence-aligned interaction matrices, normalized to a range between 0 and 1. This value contains significant information about the overall similarity of two interfaces, and is sensitive to small changes; it also necessarily encodes the more basic information about the fraction of preserved residues (FIG. 4A). To calculate the PSS for two chains or two crystals, the process is essentially repeated on a larger scale. Each interface in one chain is matched with an interface in the second chain with which it has the highest PSS. Interfaces are ordered in this way, and the individual interaction matrices are then inscribed into the larger chain/chain or crystal/crystal interaction matrix. The Frobenius product of this matrix is then taken. However, since best-matches are not necessarily reciprocal, the best-interface-matching process is repeated in reverse to ensure reciprocality of the chain or crystal PSS. The Frobenius products of the two matrices are added and then normalized to give the chain or crystal PSS.

FIGS. 4A-4C show statistics from application of this analytical scheme to all crystal structures in the PDB (39,208 entries). The average number of total, proper, and non-proper interfaces per protein molecular are 6.9, 1.8, and 5.1, respectively (FIG. 5A). While a minimum of four interfaces are required for a single molecule to form a 3-dimensional lattice, fewer are possible when multiple molecules are present in the crystallographic asymmetric unit. Proteins generally contain only a small number of interfaces beyond the minimum required for lattice formation, indicating that most interfaces contribute to structural stabilization of the lattice. On average, 50% of surface-exposed residues and 36% of all residues participate in interprotein packing interactions (FIG. 5B). While interfaces range widely in size, 36% of all interfaces and 42% of non-proper interfaces contain 10 or fewer residues counting contributions from both sides of the interface (˜5 from each participating molecule) (FIG. 5C). The small size of the average interface is encouraging relative to the feasibility of engineering interface formation. Half of all interfaces are under eight residues in size, and a quarter (8678 total) are under eight residues in range within the polypeptide chain (separation). The cumulative size/range distributions for all interfaces, CBIEs, and EBIEs (FIG. 5D) shows that most interfaces are topologically simple and local in the primary sequence, even though some are complex. It is noteworthy that FBIE's contain on average fewer than two EBIEs (not shown) and that most EBIEs are less than 4 residues in size and 10 residues in range. These small EBIEs represent prime candidates for engineering improved crystallization of crystallization-resistant proteins.

Quantifying similarity in the crystal-packing interactions of homologous proteins demonstrates pervasive polymorphism in interprotein interfaces. A general method was developed to quantify the similarity between different interprotein packing interfaces formed by homologous proteins. Its foundation is a B-factor-weighted count (C_(ij)) of inter-atomic contacts between residues i and j across the interface:

$C_{ij} = {\sum\limits_{{atom}.{pairs}}\left( \frac{< B >_{2 - {10\%}}}{\sqrt{B_{m}B_{n}}} \right)^{n}}$

The terms B_(m) and B_(n) are the atomic B-factors of the contacting atoms in residues i and j, respectively (i.e., atoms with centers separated by less than 4 Å), while <B>_(2-10%) represents an estimate of the B-factor of the most ordered atoms in the structure (which is calculated as the average B-factor of atoms in the 2nd through 10^(th) percentiles). An upper bound of 1.0 is imposed on the B-factor ratio (i.e., it is set to 1.0 whenever (B_(m)B_(n))^(1/2)<<B>_(2-10%)). The exponent n is an adjustable parameter in our software that allows analyses to be performed either without (n=0) or with (n≥1) down-weighting of contacts between atoms with high B-factors. Such atoms, which have enhanced disorder, may contribute less to interface stabilization, but prior literature on this topic is lacking. Therefore, we developed an analytical approach facilitating exploration of B-factor effects. Specifically, using higher values of n in our scoring function progressively down-weights high B-factor contacts.

Each interface in a crystal structure (as defined above) is quantitatively described by a contact matrix C containing the corresponding C_(ij) values (i.e., with its rows and columns indexed by the residue numbers in the two interaction proteins). To evaluate the similarity in interprotein interfaces formed by homologous proteins, their sequences are aligned using the program CLUSTAL-W (Mateja, Acta crystallographica 2002, 58 (Pt 12), 1983-91) (after transitively grouping together all proteins sharing at least 60% sequence identity). This procedure effectively aligns both the columns and rows in the contact matrices for interfaces formed by the homologous proteins. The Packing Similarity Score (PSS) between the interfaces is then calculated as the Frobenius (matrix-direct) product between the respective contact matrices. This procedure is mathematically equivalent to calculating a dot-product between vectors filled with the contact count between residue pairs in the interfaces. PSSs value ranges from 1.0, if the number of contacts between each interfacial residue pair is identical, to 0.0, if no pairwise contacts are preserved.

This metric was used to analyze a dataset comprising all pairs of crystal structures in the PDB containing proteins with ≥98% sequence identity (FIG. 4C). This dataset includes a heterogeneous mixture of mutant/ligand-bound structures in the same spacegroup as well as alternative crystal forms of the same protein. While many interfaces are approximately conserved, it is rare for identical packing interactions to be observed in different crystal structures of nearly identical proteins. While 35% of interfaces show PSSs of 0.80-0.95, another 30% have PSSs from 0.40-0.80. Therefore, there is almost invariably some degree of plasticity in interfacial packing contacts and frequently substantial polymorphism. Importantly, the residues involved in crystal-packing interactions tend to be conserved (˜50% over random expectation) even when pairwise interactions in the interface are not conserved. This observation indicates that some surface residues have inherently high crystallization-packing potential, so introducing corresponding epitopes into a protein is likely to increase its crystallization propensity even if the complementary epitope is not present.

The observation that some interfacial contacts are preserved, while other are not, leads to a series of important conceptual and practical conclusions. Most importantly, conservation of packing similarity provides experimental data on the strength of the different packing contacts within an interface, because energetically more stable contacts are less likely to be perturbed to satisfy differences in the physiochemical environment in different crystals. The results and molecular-mechanics calculations described herein show that the more preserved packing contacts have higher thermodynamic stability than the less preserved contacts. These contacts with higher stability are likely to play an important role in specifying and stabilizing the crystal lattice, and are therefore prioritized for evaluation in epitope-engineering experiments. Some residues contribute more than others to stabilization of crystal packing-interactions in thermodynamic dissection of interprotein interfaces in stable complexes (Jaroszewski, Structure 2008, 16 (11), 1659-67). Residues making packing contacts with lower stability nonetheless need to be immobilized upon interface formation, which will incur a substantial entropic penalty that could be larger than their favorable contribution to the formation of crystal interfaces. In this context, it is not surprising that crystallization is thermodynamically finicky and very sensitive to the mean entropy of surface-exposed side chains (Derewenda, Acta crystallographica 2006, 62 (Pt 1), 116-24).

Mutation of surface-exposed residues is likely to induce changes in crystal packing whether they participate in either high-stability or low stability contacts. This effect, combined with the fact that 60% of the surface-exposed residues in the average protein make interfacial contacts (FIG. 5A), rationalizes the fact that surface mutations very frequently change crystallization behavior and that proteins with less than 90% sequence identity only form similar non-proper packing interfaces very infrequently (FIG. 5C). However, engineering improved crystallization behavior requires introduction of epitopes with a propensity to form high-stability crystal-packing contacts.

Creation of a library of all linear sequence epitopes mediating crystal-packing interactions in the PDB and to develop metrics to score their packing potential. We have created a database containing a library of all EBIEs, CBIEs, and FBIEs in the PDB that span at most two successive regular secondary structural elements and flanking loops (as identified by the DSSP algorithm (Wukovitz, Nat Struct Biol 1995, 2 (12), 1062-7)). The sequence of both contacting and non-contacting residues is stored along with the standard DSSP-encoding of the secondary structure at each position in the protein structure in which the epitope was observed to mediate a crystal packing interaction. All metrics possibly related to the crystal-packing potential of the epitope are recorded, including B-factor distribution parameters, statistical enrichment scores relative to all interfaces in the PDB as well as conservation in multiple crystals from homologous proteins, and crystallization propensity and solubility scores based on the sequence composition of the epitope. The database includes the identity of all EBIE pairs making contact with each other as well as a breakdown of the composition of all FBIEs and CBIEs in terms of their constituent EBIES.

Computational analyses of crystal-packing interactions in the PDB to identify short epitopes with statistically enhanced occurrence in crystal-packing interfaces. This library is used to count all EBIEs which appear in the PDB, and to determine which sequences are statistically overrepresented in EBIE's given their background frequency in non-interacting sequences in the PDB.

Prior to considering specific amino acid sequences, the secondary structure patterns which appeared most frequently in EBIEs were examined. Some secondary structure patterns appeared much more frequently than others; these are summarized in Table 2.

Example 6 Epitope-Engineering Experiment.

The methods described herein were used to select putative crystallization-enhancing epitopes for six target proteins that yielded unsolvable crystals and another three that never yielded crystals of any kind with their native sequences (FIG. 9 & FIGS. 10A-10F). After making an average of three epitope mutations per protein, crystal structures were obtained for five of the six proteins that yielded unsolvable crystals with their native sequences (FIG. 9). Furthermore, crystals for two of the four proteins that failed to yield any crystals with their native sequences were also obtained. Both 1.9 Å and 1.8 Å diffraction was obtained for these two proteins respectively, and both datasets led to solved crystal structures (FIGS. 16-17). All of the amino-acid substitutions that produced crystal structures involved substitution of a residue with higher sidechain entropy than the residue it replaced in the native sequence. In three cases, the successful mutation involved introduction of lys or glu residues, exactly the residues that are removed in classic surface-entropy reduction. Therefore, while engineering low surface entropy is one consideration underlying the methods described herein, the design strategy focusing on tertiary epitopes leads to fundamentally different kinds of amino acid substitutions than used in previous surface-entropy reduction methods involving substitution of individual amino acids with low sidechain entropy, which are generally more hydrophobic and impair protein solubility. In contrast, in the results described herein, 39 of 41 mutant proteins (95%) were sufficiently stable and soluble to undergo high-throughput crystallization screening (FIGS. 10 A and B). Only two of these were significantly destabilized compared to the native sequence based on Thermofluor analyses (FIG. 10C). The vast majority produced a significant increase in the number of crystallization hits in systematic high-throughput screening (FIG. 10D). One crystal structure was obtained from a mutant that reduced the total number of hits but produced hits under alternative chemical conditions. This property was shared by 28 of 32 screened mutant proteins, i.e., they yielded at least some and typically many “hits” under alternative conditions than the WT protein (FIG. 10E). Two of the five crystal structures generated from mutant proteins show the mutated residue making a direct contact in a packing interface (e.g., FIG. 10F), although with somewhat different stereochemistry from the template used for engineering. The third structure shows the mutant residue contacting an adjacent residue that makes a crystal packing contact. However, the fourth structure shows the mutant residue in a region of weak electron density, while the fifth shows it to be relatively remote from any packing interface.

An advantage of the methods described herein is its very high yield of soluble protein variants, which enable the search for chemical conditions mediating stable lattice formation to be conducted with proteins with a greater diversity of surface properties that are generally favorable for crystallization. This new crystallization-screening “variable”, which can be explored efficiently with the methods describes herein, enables more effective exploitation of the thermodynamic forces promoting crystallization during extensive chemical screening.

Example 7

C-3.4. MESUSA-Calculated Interaction Energies Differ Significantly for Conserved Vs. Non-Conserved Packing Contacts.

An initial evaluation of the efficacy of molecular mechanics calculations in identifying stabilizing crystal-packing epitopes in the PDB was performed. This analysis employed MEDUSA, a comprehensive protein design toolkit.

The MEDUSA molecular design toolkit employs an all-atom force-field to model each protein residue using a united atom model including all heavy atoms and polar hydrogens. Local interactions are modeled using the Dunbrack backbone-dependent rotamer library, and the free energy of a protein is expressed as a weighted sum of van der Waals, solvation, H-bonding and backbone-dependent statistical energies. Because MEDUSA is not trained using experimental data, the force-field is transferable to multi-protein complexes. The free energies of individual proteins and protein-protein complexes are calculated using MEDUSA's “fixed backbone redesign tool”, which samples sub-rotameric sidechain states using Monte Carlo simulated annealing. In modeling interface formation, residues within 7.5 Å of any atom across the interface of the complex are considered. In order to account for side chain entropy changes, we perform at least 20 individual interface minimization runs and consider the average free energy for the individual terms in the equation. The terms in the energy function are decomposed and used to compute a linear sum of components to obtain the free energy changes associated with each residue upon interface formation. Other molecular toolkits can also be used in connection with the methods described herein, including, but not limited to methods that include solvent molecules in modeling interprotein interfaces. Such toolkits, identify interfacial residues with unsatisfied H-bonds and dynamically places one or more water molecules in close proximity to the identified residues to facilitate H-bond formation. When present, crystallographically observed solvent molecule positions can be used to guide initial placement. Use of toolkits that include solvent molecules in modeling interprotein interfaces can improve the accuracy in estimating the free energy of interface formation compared to the results in FIGS. 10A-10F. The utility of free energy calculations in MEDUSA can be used to predict alterations in the stability of epitope-engineered proteins as well as possible perturbations in the stability of inter-epitope interactions due to amino acid context. While structures will not be available for proteins undergoing epitope engineering, they are available for the proteins in which these epitopes were previously observed to mediate crystal-packing interactions. The epitope-engineering methods described herein can be used to prioritize introducing epitopes into a defined super-secondary structural element predicted to match that in which the candidate epitope was previously observed. The crystal structures of these proteins can be used to estimate the effect of the local amino acid context in the protein of unknown structure on both the self-interaction energy of the epitope and the interfacial interaction energy of the epitope in all structures in which it was previously observed to mediate crystal-packing contacts. When averaged over all proteins in the PDB containing the candidate epitope, this stereochemical and energetic model can capture unfavorable local stereochemical interactions as well as potential interference of proximal residues with previously observed crystal-packing contacts. Therefore, MEDUSA can be used to estimate the energetic effects of all neighboring residues within ±4 residues of the mutated positions in the target protein. Such mutations can be introduced as in silico mutations in the proteins of known structure in which the epitope was previously observed to mediate crystal-packing contacts. Known methods (Yin et al., Structure 2007, 15, 1567-1576; Gilis and Rooman, Journal of molecular biology 1997, 272 (2), 276-90; Yin et al., J. Chem. Infor. and Model 2008, 48, 1656-1662) can be used to estimate the impact of this set of mutations on the stability of the protein of known structure, and the methods described above will be used to estimate its effect on the free energies of formation of the previously observed crystal-packing interactions containing the epitope. These computational results can be compared with the experimental results acquired according to the methods described herein to determine whether these MEDUSA calculations show statistical utility for guiding epitope-engineering efforts.

MEDUSA was benchmarked on experimental data comprising 595 point mutations in five structurally unrelated proteins (Yin et al., Structure 2007, 15, 1567-1576). MEDUSA optimized packing of the mutated protein via sidechain rotamer sampling. The lowest energy from multiple runs was used to compute mutant stability, and the stability change (ΔΔG) was obtained by subtracting the energy of the wild type protein from that of the mutant. These studies demonstrated good agreement with experimental data (r=0.75, p=2×10⁻¹⁰⁸). This correlation level is comparable to that from heuristic models whose parameters are trained using experimental data (Gilis and Rooman, Journal of molecular biology 1997, 272 (2), 276-90; Bordner et al., Proteins 2004, 57 (2), 400-13; Guerois, et al., Journal of molecular biology 2002, 320 (2), 369-87; Saraboji, et al., Biopolymers 2006, 82 (1), 80-92), even though the interaction parameters used by MEDUSA were not trained in this way. Therefore, the observed results indicate that the force field can be transferable to multi-protein and protein-small molecule complexes and that MEDUSA is a suitable tool for estimating the stability of interprotein packing interfaces.

The data presented in FIGS. 11A-11B show that calculated interfacial interaction energies from MEDUSA significantly correlate with the preservation of inter-residue packing interactions in existing crystal structures. This analysis was performed on 118 interfaces from proteins for which at least two crystal structures have been deposited in the PDB with ≥98% sequence identity. Interfaces were chosen from this set at random to provide a homogenous distribution of both interface size (7-60 residues) and PSS (0.0-1.0) relative to the most similar interface in ahomologous crystal structure. In other words, each bin in interface size in the analyzed subset has an equivalent distribution in PSS and vice-versa. The free energy of interface formation was calculated using MEDUSA by subtracting the calculated free energies of both separated interfaces from their calculated free energy in the complex. This approach should accurately model the loss in sidechain entropy upon interface formation. However, interfacial solvent molecules were excluded from this preliminary calculation, even though their inclusion is likely to increase accuracy, because the methods required to accurately estimate their free energy contribution are still being implemented in MEDUSA. Accurate treatment of such species can further modeling of interfacial hydrogen-bonding (H-bonding) networks can be performed using toolkits that identify interfacial residues with unsatisfied H-bonds and dynamically places one or more water molecules in close proximity to the identified residues to facilitate H-bond formation. FIG. 11A shows that there is a significant correlation between the calculated free energy change of each individual amino acid in all 118 interfaces and its PSS relative to a homologous structure (as calculated for a single residue using the same mathematical formalism described above for the entire interface). Residues with more favorable calculated free-energy gains upon interface formation have a tendency to be more conserved in multiple crystals. While the slope of the correlation is modest, its statistical significance is high (p=0.0013). Importantly, residues showing calculated free energy changes better than −1.35 kcal/mole upon interface formation always show at least partial preservation of their contacts in multiple crystals in this dataset (FIG. 11B), indicating that this threshold can be used to reliably distinguish residues making energetically favorable packing interactions. Therefore, even without modeling interfacial water molecules, MEDUSA shows efficacy in identifying preserved crystal-packing interactions in an experimental dataset. These results indicate that MEDUSA is a can be used for identifying high-quality packing epitopes for evaluation in the crystallization engineering experiments proposed below

The methods described herein can be adapted to perform analyses related to protein solubility to evaluate whether they are predictive of crystallization outcome. In addition to changes in total and mean hydrophobicity, the predicted influence of the mutations on expression/solubility can be determined according to the P_(ES) metric described herein.

The methods described herein can also be adapted to implement one of several previously published “correlated evolution” metrics (Liu, et al., Bioinformatics 2008, 24 (10), 1243-50; Eyal, et al., Bioinformatics 2007, 23 (14), 1837-9; Hakes, et al., PNAS 2007, 104 (19), 7999-8004; Kann, J Mol Biol 2009, 385 (1), 91-8; Kann, Proteins 2007, 67 (4), 811-20) to examine anti-correlations of the proposed mutations with residue identity at other positions in the sequence. Such anti-correlations can be used to predict reduced stability of mutant proteins.

Because some mutations can eliminate existing epitopes favorable for crystallization in the process of introducing a new epitope, methods to explicitly identify all lost epitopes and evaluate whether such losses reduce the probability of improving crystallization outcome and also be used in connection with the methods described herein.

An output describing the predicted surface-exposure of the mutated residues and also be used in conjunction with the methods described herein. Thus surface-exposure can be considering the sequence variations in homologs as well as by incorporating predictions from PHD/PROF.

B-factor distributions in sub-epitopes can also be evaluated as a function of overrepresentation ratio, structure resolution, residue type, epitope size, buried surface area, and proportional contribution to an interface in connection with the methods described herein. Such analysis can be used to design of ranking metrics using sub-epitope B-factor distributions.

Analyses of topological, energetic, and primary sequence differences between non-BIOMT/non-proper crystal packing interactions and BIOMT interfaces mediating stable protein oligomerization, can also be used in connection with the methods described herein. Such analyses can be used to determine whether ranking metrics excluding BIOMT interfaces improve outcome.

Several reference databases can be generated in addition to the 2-to-6-mer sub-epitope database described herein (EEDb1). One such reference database can be used to restrict overrepresentation calculations and engineering suggestions to sub-epitopes with surface-exposed residues at all contacting positions (EEDb2). Other reference databases can be used to restrict consideration to complete EBIEs rather than including sub-epitopes (EEDb3). Yet another reference database could be limited to single amino acids in a specific secondary structure as presented in FIG. 19.

The epitope-engineering methods described herein can be adapted for alpha-helical integral membrane proteins (IMPs). This adaptation can be performed by adding a second mask to the specification of each epitope indicating whether it resides in a transmembrane alpha-helix. The epitope distributions observed in the crystal structures of alpha-helical IMPs can be compared to those in the full PDB and the distribution of packing contacts relative to the centroids and the termini of the transmembrane α-helices can be analyzed. The observed patterns can be used to customize epitope-engineering suggestions for a-helical IMPs.

Example 8 Introduction of Salt Bridges Improve Crystallization

One of the most overrepresented dimeric crystallization sub-epitopes in the PDB comprises a glu-arg salt-bridge on the surface of an α-helix (ExxxR/HHHHH in Table 37). Introduction of this sub-epitope into predicted alpha-helices in crystallization-resistant proteins can improve their crystallization sufficiently to yield a structure.

Four NESG proteins that have given crystals with at best poor diffraction (4-8 Å limiting resolution at the synchrotron) and another four that have never given a crystallization hit were selected for analysis. These eight proteins were mutated to introduce new glu-arg salt-bridges at 4 different sites in predicted alpha-helices. The mutant proteins were expressed and analyzed for their solubility, stability, and hydrodynamic homogeneity and subjected to crystallization screening and optimization using the standard NESG platform. All related experimental data were systematically evaluated to determine whether any of the sequence parameters and computational metrics correlated with outcome at every stage of the pipeline (i.e., expression, solubility, stability, and crystal-structure solution.)

Example 9 Introduction of Other Epitopes Improve Crystallization

Similarly designed studies will be conducted on four other highly overrepresented dimeric sub-epitopes shown in Table 37. Another study will focus on introducing 20 different candidate sub-epitopes into each of two poorly crystallizing proteins to evaluate correlations between protein expression/crystallization outcome and all computed ranking metrics. Another study will take a similar approach to determining whether efficacy is improved by limiting engineering to complete EBIEs rather than using sub-epitopes. Based on the results obtained from these initial studies, additional studies will be designed to further explore the efficacy of alternative crystallization-epitope-engineering strategies.

Example 10 Effects of Epitope Engineered Single and Poly Mutant Proteins on Protein Solubility

The introduction of crystallization-inducing epitopes can also have effects on other protein characteristics, such as solubility. To compare the solubility of the wildtype protein VCR193 to its epitope mutants, each VCR193 construct was subjected to a precipitant solution of ammonium sulfate at varying concentrations, and after a period of incubation, soluble protein levels tested with a NanoDrop 200 UV-Vis Spectrophotometer.

All protein stock concentrations were determined using the NanoDrop 2000 at A280. A stock solution of precipitant (3M NH4SO4) was prepared in Experimental buffer (50 mM sodium acetate, pH 4.25). Using these stock concentration values, mixtures of varying protein and precipitant concentrations were prepared in 1.5 mL Eppendorf tubes at room temperature. For each construct, final protein concentrations of 1, 2 and 4 mg/mL were mixed with final precipitant concentrations of 0.8, 1.0, 1.2 and 1.4M NH4SO4. Experimental buffer was used to bring each aliquot to a final volume of 50 uL. For all samples, components were introduced in the order of precipitant, buffer, and protein. All samples were performed in duplicate. Once all mixtures were prepared, samples were incubated at room temperature for 5 minutes, then transferred to a benchtop microcentrifuge. Samples were spun for 2 minutes at 13.4K RPM to pellet any precipitation. Sample supernatants were then tested for remaining soluble protein with the NanoDrop 2000.

Results show that for the 4 single mutants designed for VCR193, only one (VCR193_F241R) had a detrimental effect on protein solubility (FIG. 13). Notably, the mutation reducing solubility was the only one among the set tested to significantly destabilize the protein thermodynamically. All other mutants maintained, or showed a slight increase (VCR193_V122R) in protein solubility.

Similar results were seen for the poly-mutant samples (FIG. 14). Protein solubility was not affected, except in the one poly mutant that contained the VCR193_F241R mutation which had previously shown a decrease in solubility.

Example 11 Combining Multiple Epitope Mutations can Produce Additional Large Gains in Crystallization Propensity Over the Individual Constituent Mutations

Purified proteins were set up in a standard robotic microbatch crystallization screen. The screen covered 1536 different chemical conditions. Observations were reported after one week of incubation at 4° C., based on robotic imaging of the reactions and manual evaluation of the resulting optical micrographs. The results in FIG. 15 demonstrate that the epitope mutations in this protein generally increase the number of crystallization hits and always yield hits under different crystallization conditions than the WT protein. Combining multiple epitope mutations increases further the number of hits obtained, indicating that this “multimutant” crystallizes more avidly than the individual epitope mutant.

Example 12 Epitope-Engineering Study on “No Hits” Proteins.

Proteins were selected with Pxs≥0.25, monodisperse stocks, and clean Thermofluor melts. Four proteins that showed no evidence of crystallization with their native sequences in the 1536 well screen were re-purified and put through the 1536 well screen a second time, to verify their failure to crystallize prior to the generation of mutants. Four or five epitope mutations, primarily introducing salt-bridges, were then introduced into each protein, and the resulting mutant variants were purified and analyzed, yielding results summarized in FIG. 16. Of the 18 mutations for which data are presented, 16 essentially preserved the stability and solubility of the protein. Single epitope mutations yielded very high quality crystal structures for two of the four proteins in the study. The results show that epitope mutations producing crystal structures are located in packing contacts. The mutated residues make direct or water-mediated hydrogen-bonds in one of the crystal-packing interfaces in these structures, as shown for protein LpYceA (LgR82) in FIG. 17 on the right. Any failures were either large (>400 aa) or yielded aggregation-prone proteins upon mutation. Additional epitope mutations can be introduced into stable di- and tri-mutants of failures.

Example 13 Overrepresentation of Individual Amino Acids in Specific Secondary Structures in Packing Interfaces in the PDB.

After normalization for the abundance of the amino acids on protein surfaces in the PDB (“surface-shaping”), the number of amino acids in each secondary-structure class making crystal-packing interactions was counted and compared to random expectation. FIG. 19 shows the over-representation ratios calculated in this manner for the 60 classes (20 amino acids in three possible secondary structures—H, E, and L for helix, strand, and “loop”, respectively). FIG. 20 presents the same values plotted against the solvent-accessible surface area of the sidechain of each amino acid, which shows that amino acids with comparable surface area have significantly different propensity to mediate crystal-packing interactions. Notably, many of the most strongly overrepresented residues in crystal-packing interfaces have a negative influence (e.g., gln, glu, or lys in helices) or a neutral influence (arg in helices) on crystallization propensity when overall amino-acid-frequency on the protein surface is analyzed. Therefore, the data presented in these slides demonstrate that the structural context of individual amino acids has a critical effect on their propensity to mediate crystal-packing interactions. These results demonstrate that the epitope library described herein is successful in identifying the proper context, as evidenced by the data obtained in experiments introducing these epitopes into crystallization-resistant proteins. This context frequently involves high-entropy polar side chains being constrained by local entropy-reducing structural interactions. Notably, the amino acids substitutions that have been most successful in yielding crystal structures in these experiments (i.e., glu and arg in helices) are among the most strongly overrepresented in crystal-packing interfaces once secondary structure is taken into account, as shown in FIG. 19. Therefore, one reason that our methods are successful in improving protein crystallization is that they guide insertion at productive locations of amino acids that have a high propensity to mediate crystal-packing interactions when present in the right structural context.

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APPENDIX A

TABLE 4 Se- Struc- In Expected in P-Value P-Value Distri- Observed Null quence ture Epitopes Epi In PDB Z-Score Upper Lower bution Ratio Probability R H 73875.0 56304.4 135926.2 96.749968 0.0000e+00  1.00000 N 0.543493 0.414228 E H 102063.2 85694.0 211404.9 72.514212 0.0000e+00  1.00000 N 0.482785 0.405355 R C 71101.6 59909.4 138577.7 60.689664 0.0000e+00  1.00000 N 0.513081 0.432316 Q H 48815.1 39519.7 106533.5 58.954888 0.0000e+00  1.00000 N 0.458214 0.370961 K H 75386.1 65574.6 154046.4 50.558309 0.0000e+00  1.00000 N 0.489373 0.425681 R E 31731.5 25548.4 65634.9 49.498779 0.0000e+00  1.00000 N 0.483455 0.389250 Y C 29955.1 25200.3 79918.7 36.198231 3.7253e−287 1.00000 N 0.374820 0.315324 Y H 22863.8 18907.6 77770.4 33.070975 4.4619e−240 1.00000 N 0.293991 0.243121 N C 74926.0 68249.9 172909.9 32.846465 6.9358e−237 1.00000 N 0.433324 0.394714 Y E 20348.1 16817.5 77792.9 30.751543 6.6667e−208 1.00000 N 0.261568 0.216182 H H 17545.3 14723.1 46812.1 28.092472 6.9628e−174 1.00000 N 0.374803 0.314515 W C 9843.2 7836.3 28898.7 26.555390 1.3266e−155 1.00000 N 0.340610 0.271165 W E 7175.4 5519.1 28478.8 24.830813 2.5110e−136 1.00000 N 0.251956 0.193796 N H 29380.1 26250.3 74966.1 23.963336 3.6776e−127 1.00000 N 0.391912 0.350162 Q C 46688.9 43067.7 104526.3 22.756429 6.6571e−115 1.00000 N 0.446671 0.412027 D H 48052.3 44330.5 115744.8 22.503742 2.0419e−112 1.00000 N 0.415157 0.383002 Q E 16054.3 13925.4 44387.5 21.776876 2.1490e−105 1.00000 N 0.361685 0.313724 E E 27514.1 24818.0 68285.5 21.450513 2.4598e−102 1.00000 N 0.402927 0.363444 K C 84342.9 80316.9 179173.6 19.124939 8.1926e−82  1.00000 N 0.470733 0.448263 W H 8266.4 6969.2 34240.4 17.410753 3.8441e−68  1.00000 N 0.241422 0.203539 F C 25086.1 22981.3 88412.8 16.139207 7.1968e−59  1.00000 N 0.283738 0.259932 P H 20437.9 18997.4 55888.0 12.864046 3.7994e−38  1.00000 N 0.365694 0.339919 K E 30928.1 29266.2 72555.6 12.576763 1.4865e−36  1.00000 N 0.426268 0.403362 H E 9540.2 8591.3 33198.0 11.890730 7.1273e−33  1.00000 N 0.287373 0.258790 F E 14087.0 13074.4 85656.9 9.620803 3.4203e−22  1.00000 N 0.164458 0.152636 E C 80396.1 78595.3 181587.9 8.529403 7.5074e−18  1.00000 N 0.442739 0.432822 X H 360.8 254.8 654.5 8.497762 1.3638e−17  1.00000 N 0.551261 0.389301 X E 156.4 96.6 287.5 7.471589 6.3554e−14  1.00000 N 0.544000 0.335882 X C 819.5 684.6 1607.8 6.803125 6.0965e−12  1.00000 N 0.509703 0.425809 F H 16970.0 16250.6 93022.4 6.212142 2.6862e−10  1.00000 N 0.182429 0.174695 D C 92573.2 91722.3 226663.0 3.641120 1.3686e−04  0.99987 N 0.408418 0.404664 N E 12244.9 11913.0 40730.7 3.614854 1.5345e−04  0.99985 N 0.300631 0.292483 S H 34149.8 34223.3 112014.7 −0.476652 0.68435 0.31796 N 0.304869 0.305525 C C 8790.4 8862.7 38092.8 −0.876297 0.81121 0.19209 N 0.230763 0.232660 D E 13940.8 14199.4 46856.3 −2.599200 0.99540 4.7409e−03  N 0.297522 0.303041 M H 11582.9 12155.3 61070.7 −5.801564 1.00000 3.3857e−09  N 0.189664 0.199037 M E 5267.8 5774.1 33368.7 −7.327132 1.00000 1.2408e−13  N 0.157867 0.173040 P E 7858.0 8602.7 29317.0 −9.552002 1.00000 6.7668e−22  N 0.268036 0.293438 C H 3384.9 4013.8 27016.9 −10.757787 1.00000 2.9878e−27  N 0.125288 0.148566 T H 25364.6 26858.9 95207.8 −10.761143 1.00000 2.7304e−27  N 0.266413 0.282108 P C 79479.4 82017.5 226569.8 −11.095397 1.00000 6.7670e−29  N 0.350794 0.361997 C E 3054.0 3879.2 30999.5 −14.164659 1.00000 8.5647e−46  N 0.098518 0.125137 I C 24372.0 26598.2 100435.4 −15.920127 1.00000 2.4323e−57  N 0.242663 0.264829 T C 60897.2 64345.5 175852.7 −17.071578 1.00000 1.2602e−65  N 0.346297 0.365906 S E 18279.6 20897.6 82683.2 −20.949793 1.00000 1.0248e−97  N 0.221080 0.252742 L C 48520.1 52756.1 185873.9 −21.792493 1.00000 1.4458e−105 N 0.261038 0.283827 T E 25710.1 29024.2 103538.7 −22.930572 1.00000 1.2467e−116 N 0.248314 0.280322 I E 18320.0 21510.1 141124.2 −23.626283 1.00000 1.1296e−123 N 0.129815 0.152420 I H 19655.0 23276.8 135724.2 −26.080376 1.00000 3.3441e−150 N 0.144816 0.171501 L H 45000.3 51092.6 272207.2 −29.904831 1.00000 9.1633e−197 N 0.165316 0.187697 A H 52051.2 58421.3 249208.6 −30.120751 1.00000 1.3919e−199 N 0.208866 0.234427 G E 8765.5 11960.8 69614.7 −32.104668 1.00000 2.2298e−226 N 0.125914 0.171814 L E 20637.7 25409.3 157007.0 −32.696540 1.00000 9.7828e−235 N 0.131444 0.161835 V H 21098.2 25866.6 140167.6 −32.832062 1.00000 1.1500e−236 N 0.150521 0.184540 M C 16433.8 20329.4 60211.0 −33.571201 1.00000 2.5524e−247 N 0.272937 0.337636 V C 33470.7 39146.4 134145.5 −34.088036 1.00000 6.1460e−255 N 0.249510 0.291820 V E 26733.1 32838.8 197868.3 −36.893349 1.00000 3.3022e−298 N 0.135106 0.165963 A E 10155.7 14278.8 89436.9 −37.640052 1.00000 0.0000e+00  N 0.113552 0.159652 G H 13372.0 17828.1 78310.4 −37.975062 1.00000 0.0000e+00  N 0.170756 0.227659 S C 79747.1 88923.2 239515.9 −38.807598 1.00000 0.0000e+00  N 0.332951 0.371262 H C 30625.2 38464.2 98652.4 −51.171809 1.00000 0.0000e+00  N 0.310435 0.389896 A C 50800.4 63066.5 189640.9 −59.786078 1.00000 0.0000e+00  N 0.267877 0.332557 G C 105444.1 123958.6 348901.2 −65.492096 1.00000 0.0000e+00  N 0.302218 0.355283

TABLE 5 In Expected in P-Value P-Value Observed Null Sequence Structure Epitopes Epi In PDB Z-Score Upper Lower Distribution Ratio Probability LP CC 3644.5 2731.7 19983.1 18.795754 4.9663e−79 1.00000 N 0.182379 0.136702 GY CC 1961.0 1370.5 8928.0 17.337729 1.5760e−67 1.00000 N 0.219646 0.153503 PN CC 2684.8 2018.2 10016.5 16.605426 3.9173e−62 1.00000 N 0.268038 0.201486 GK CH 497.2 251.2 2101.1 16.539879 1.6538e−61 1.00000 N 0.236638 0.119564 DG CC 5443.5 4486.7 22101.7 16.001152 7.1729e−58 1.00000 N 0.246293 0.203000 PG CC 5008.5 4096.2 20210.3 15.962799 1.3350e−57 1.00000 N 0.247819 0.202681 GF CC 1762.8 1246.3 9499.7 15.696619 1.0133e−55 1.00000 N 0.185564 0.131193 NG CC 4061.8 3269.8 16386.4 15.481858 2.6772e−54 1.00000 N 0.247876 0.199541 YP CC 1468.8 1031.4 7236.3 14.706553 3.7500e−49 1.00000 N 0.202977 0.142537 FP CC 1415.6 1047.9 8539.3 12.127760 4.6029e−34 1.00000 N 0.165775 0.122713 FG HC 520.5 323.3 2395.3 11.793909 2.9912e−32 1.00000 N 0.217301 0.134962 PF CC 1170.4 855.8 6117.8 11.594115 2.7366e−31 1.00000 N 0.191311 0.139893 PE HH 2240.3 1801.5 9246.3 11.522645 5.9070e−31 1.00000 N 0.242292 0.194830 TE CH 705.0 481.3 2274.8 11.486097 1.0424e−30 1.00000 N 0.309917 0.211561 CW HH 58.9 15.3 364.3 11.413216 8.0109e−30 1.00000 N 0.161680 0.041888 AA HC 564.4 371.6 2472.5 10.852231 1.3234e−27 1.00000 N 0.228271 0.150281 GI CC 2094.8 1687.9 12350.9 10.658937 9.1167e−27 1.00000 N 0.169607 0.136663 SA CH 566.6 375.7 2576.3 10.654750 1.1178e−26 1.00000 N 0.219928 0.145839 SP CH 805.4 571.9 3849.5 10.583976 2.2515e−26 1.00000 N 0.209222 0.148553 AG CC 4357.5 3776.5 21005.1 10.439477 8.9976e−26 1.00000 N 0.207450 0.179789 PD CC 3504.6 3007.0 14606.8 10.183074 1.3107e−24 1.00000 N 0.239929 0.205862 TG HC 658.1 458.6 2835.1 10.172532 1.7080e−24 1.00000 N 0.232126 0.161773 EG EC 541.4 366.0 1983.9 10.152241 2.1774e−24 1.00000 N 0.272897 0.184487 GL CC 3403.1 2910.1 19636.5 9.902246 2.2501e−23 1.00000 N 0.173305 0.148198 KY HC 311.9 189.1 1051.9 9.856121 4.8051e−23 1.00000 N 0.296511 0.179808 SG HC 534.7 365.2 2104.2 9.758078 1.1308e−22 1.00000 N 0.254111 0.173547 GW CC 570.9 392.3 2987.4 9.677790 2.4410e−22 1.00000 N 0.191103 0.131303 WG EC 172.1 86.3 1245.8 9.578986 8.3974e−22 1.00000 N 0.138144 0.069246 PD HH 821.7 610.6 3126.7 9.525628 1.0190e−21 1.00000 N 0.262801 0.195271 AS HC 387.0 252.5 1734.3 9.157518 3.6376e−20 1.00000 N 0.223145 0.145589 SL CH 583.4 412.7 2949.5 9.062412 8.1350e−20 1.00000 N 0.197796 0.139911 SF EE 484.7 327.4 4548.1 9.020955 1.2109e−19 1.00000 N 0.106572 0.071997 RG HC 457.7 315.6 1580.9 8.942867 2.5195e−19 1.00000 N 0.289519 0.199616 DH HC 131.5 66.4 320.4 8.971856 2.7193e−19 1.00000 N 0.410424 0.207256 GN CC 3035.8 2625.3 13860.2 8.899244 3.0996e−19 1.00000 N 0.219030 0.189411 IP CC 1766.5 1451.4 11589.5 8.843319 5.2673e−19 1.00000 N 0.152422 0.125234 PQ HH 721.3 536.6 2873.3 8.841693 5.8387e−19 1.00000 N 0.251035 0.186753 WC CC 77.2 30.3 378.1 8.889715 7.1536e−19 1.00000 N 0.204179 0.080088 RH HC 196.1 112.6 557.9 8.813158 9.7271e−19 1.00000 N 0.351497 0.201757 FS EE 472.3 320.3 4887.3 8.783719 1.0221e−18 1.00000 N 0.096638 0.065543 GP CC 2507.2 2140.1 12837.1 8.692764 1.9628e−18 1.00000 N 0.195309 0.166713 HP CC 1325.0 1066.2 6355.9 8.687762 2.1421e−18 1.00000 N 0.208468 0.167751 PY CC 1128.9 891.7 5689.8 8.651118 2.9912e−18 1.00000 N 0.198408 0.156714 ER HC 439.9 308.0 1352.8 8.554820 7.8140e−18 1.00000 N 0.325177 0.227648 TN CC 1752.7 1460.3 7607.1 8.511975 9.6926e−18 1.00000 N 0.230403 0.191966 HP CH 402.9 273.6 1780.6 8.500886 1.2479e−17 1.00000 N 0.226272 0.153628 YS CC 1057.0 832.5 5270.8 8.480789 1.3152e−17 1.00000 N 0.200539 0.157938 VG EC 490.3 341.1 4028.2 8.443476 1.9615e−17 1.00000 N 0.121717 0.084679 CH CC 252.4 156.4 1105.1 8.287375 8.3120e−17 1.00000 N 0.228396 0.141505 GS CE 476.8 337.3 2322.9 8.216422 1.3394e−16 1.00000 N 0.205261 0.145201 EH HC 228.4 141.7 666.7 8.208490 1.6592e−16 1.00000 N 0.342583 0.212529 PH CC 1015.5 807.7 4323.2 8.108741 3.0021e−16 1.00000 N 0.234895 0.186827 GF CE 273.1 171.4 2043.3 8.118336 3.2802e−16 1.00000 N 0.133656 0.083872 EN HC 457.8 327.9 1515.0 8.107234 3.3452e−16 1.00000 N 0.302178 0.216406 GQ CE 454.4 324.1 1751.3 8.019975 6.7904e−16 1.00000 N 0.259464 0.185043 CG CH 66.5 26.7 303.6 8.076594 7.6058e−16 1.00000 N 0.219038 0.087834 QY CC 531.1 389.0 2107.2 7.978552 9.2897e−16 1.00000 N 0.252041 0.184607 GT EE 527.6 380.8 3779.5 7.930985 1.3508e−15 1.00000 N 0.139595 0.100763 LG HC 956.8 758.9 5143.0 7.782279 4.1596e−15 1.00000 N 0.186039 0.147553 RY HC 179.4 105.7 690.9 7.786927 5.2074e−15 1.00000 N 0.259661 0.153012 CG CC 673.3 510.2 3816.1 7.756211 5.2757e−15 1.00000 N 0.176437 0.133705 NF HC 110.1 55.6 503.5 7.750356 8.0006e−15 1.00000 N 0.218669 0.110418 TS CH 275.6 181.2 1047.3 7.710340 8.6337e−15 1.00000 N 0.263153 0.173029 SV EE 859.1 668.2 9428.4 7.661490 1.0742e−14 1.00000 N 0.091118 0.070871 KH HC 254.7 167.1 760.9 7.669848 1.2101e−14 1.00000 N 0.334735 0.219625 SY CC 947.1 755.4 4608.1 7.627352 1.3977e−14 1.00000 N 0.205529 0.163932 RF HC 157.1 89.5 702.0 7.654627 1.5033e−14 1.00000 N 0.223789 0.127447 TP CH 756.7 588.2 3562.8 7.601796 1.7380e−14 1.00000 N 0.212389 0.165105 AG HC 665.7 508.3 3275.0 7.597643 1.8163e−14 1.00000 N 0.203267 0.155195 QG HC 302.1 204.5 1062.1 7.595025 2.0764e−14 1.00000 N 0.284436 0.192546 EF HC 151.8 86.1 660.5 7.589196 2.5096e−14 1.00000 N 0.229826 0.130390 GV CC 2697.8 2362.0 16253.8 7.473908 4.2358e−14 1.00000 N 0.165980 0.145319 SR CH 430.0 312.0 1576.3 7.458081 5.5765e−14 1.00000 N 0.272791 0.197943 YH HH 259.5 168.6 1432.6 7.457380 6.0182e−14 1.00000 N 0.181139 0.117657 HH HH 291.1 195.1 1319.4 7.449929 6.2606e−14 1.00000 N 0.220631 0.147834 SE CH 719.8 563.0 2748.7 7.411761 7.4454e−14 1.00000 N 0.261869 0.204817 SG EE 554.8 413.5 3653.5 7.381191 9.5407e−14 1.00000 N 0.151854 0.113168 HH HC 98.4 50.9 263.6 7.406467 1.1640e−13 1.00000 N 0.373293 0.193191 ES EE 396.4 281.8 2060.3 7.349239 1.2662e−13 1.00000 N 0.192399 0.136766 QY HC 142.8 81.9 492.7 7.372573 1.3154e−13 1.00000 N 0.289832 0.166190 WP CC 391.6 276.7 2395.3 7.342160 1.3337e−13 1.00000 N 0.163487 0.115532 EN EC 274.9 184.8 998.5 7.339252 1.4549e−13 1.00000 N 0.275313 0.185106 NN CC 1908.0 1644.3 7974.1 7.300124 1.5931e−13 1.00000 N 0.239275 0.206200 CH HH 134.2 74.4 694.9 7.336557 1.7294e−13 1.00000 N 0.193121 0.107068 SR HC 280.3 190.0 982.7 7.294196 2.0261e−13 1.00000 N 0.285235 0.193343 SN HC 268.1 180.3 936.3 7.276429 2.3278e−13 1.00000 N 0.286340 0.192571 SQ CH 310.6 214.4 1180.7 7.259299 2.5698e−13 1.00000 N 0.263064 0.181616 SL HC 336.2 232.8 1884.9 7.239376 2.9156e−13 1.00000 N 0.178365 0.123503 YQ EC 128.8 71.9 489.2 7.264749 2.9907e−13 1.00000 N 0.263287 0.146984 NH CE 115.1 61.8 505.6 7.245883 3.5376e−13 1.00000 N 0.227650 0.122134 PA CH 367.6 262.5 1530.7 7.128794 6.4728e−13 1.00000 N 0.240152 0.171473 GE CE 635.3 493.6 2532.6 7.109712 6.9708e−13 1.00000 N 0.250849 0.194887 TG CC 3208.1 2864.2 16191.1 7.082544 7.6223e−13 1.00000 N 0.198140 0.176900 QF HC 113.5 61.6 439.7 7.122281 8.7171e−13 1.00000 N 0.258131 0.140203 NY HC 149.3 88.3 580.0 7.051042 1.3429e−12 1.00000 N 0.257414 0.152234 FT EE 494.0 365.0 5183.9 7.003659 1.5130e−12 1.00000 N 0.095295 0.070409 QS EE 288.5 196.3 1661.4 7.008085 1.5838e−12 1.00000 N 0.173649 0.118151 YN HC 175.1 108.8 647.7 6.965652 2.3708e−12 1.00000 N 0.270341 0.168011 RN HC 291.3 203.2 970.0 6.948606 2.4377e−12 1.00000 N 0.300309 0.209514

TABLE 6 In Expected in P-Value P-Value Observed Null Sequence Structure Epitopes Epi In PDB Z-Score Upper Lower Distribution Ratio Probability SxE ChH 1700.4 969.9 6349.9 25.481565 2.4624e−143 1.00000 N 0.267784 0.152747 TxE ChH 1585.3 930.3 5513.1 23.554174 8.6926e−123 1.00000 N 0.287551 0.168742 SxA ChH 850.1 421.1 3347.3 22.357026 9.2441e−111 1.00000 N 0.253966 0.125812 DxA ChH 999.6 535.7 3592.5 21.731401 8.6234e−105 1.00000 N 0.278246 0.149103 TxA ChH 715.6 354.6 2588.8 20.639026 1.1060e−94  1.00000 N 0.276422 0.136960 AxG HcC 1022.2 597.7 4368.0 18.691902 4.3518e−78  1.00000 N 0.234020 0.136825 NxA ChH 528.3 260.2 2030.4 17.797648 6.6617e−71  1.00000 N 0.260195 0.128165 DxS ChH 748.1 418.8 2698.0 17.510347 9.5251e−69  1.00000 N 0.277279 0.155210 NxE ChH 840.2 510.2 3189.6 15.940329 2.4469e−57  1.00000 N 0.263419 0.159957 DxR ChH 544.4 295.2 1961.9 15.736436 7.0040e−56  1.00000 N 0.277486 0.150465 SxS ChH 515.9 277.0 2080.1 15.419244 1.0009e−53  1.00000 N 0.248017 0.133156 SxQ ChH 428.7 217.8 1547.0 15.412393 1.1886e−53  1.00000 N 0.277117 0.140817 DxS CcC 2391.5 1816.6 11758.1 14.670190 6.0377e−49  1.00000 N 0.203392 0.154495 RxE EeE 590.6 340.3 2432.2 14.631398 1.3602e−48  1.00000 N 0.242825 0.139910 DxR CcC 1514.3 1076.2 6808.8 14.555462 3.4368e−48  1.00000 N 0.222403 0.158055 PxE ChH 750.1 466.0 2940.0 14.345884 8.1316e−47  1.00000 N 0.255136 0.158508 DxE ChH 1054.1 710.5 4231.1 14.129521 1.6724e−45  1.00000 N 0.249131 0.167933 RxE ChH 511.7 293.9 1726.9 13.949854 2.4681e−44  1.00000 N 0.296311 0.170167 TxY EeE 525.3 300.0 3697.0 13.569099 4.6027e−42  1.00000 N 0.142088 0.081150 SxG HcC 511.7 296.4 2101.8 13.496246 1.2581e−41  1.00000 N 0.243458 0.141004 DxD ChH 676.9 423.4 2579.0 13.477926 1.5116e−41  1.00000 N 0.262466 0.164158 TxQ ChH 358.8 189.9 1213.7 13.347342 1.0422e−40  1.00000 N 0.295625 0.156445 KxG HhC 794.3 518.5 3293.5 13.196235 6.3329e−40  1.00000 N 0.241172 0.157426 ExG HcC 907.8 610.7 3653.9 13.173395 8.3719e−40  1.00000 N 0.248447 0.167137 YxG EcC 388.8 209.7 2305.9 12.974743 1.3641e−38  1.00000 N 0.168611 0.090928 SxD ChH 668.8 424.4 2701.0 12.924936 2.2948e−38  1.00000 N 0.247612 0.157111 DxQ ChH 411.3 232.6 1454.6 12.781923 1.6375e−37  1.00000 N 0.282758 0.159919 ExG HhC 887.1 600.4 3922.9 12.716402 3.1827e−37  1.00000 N 0.226134 0.153038 AxG HhC 719.4 465.5 3596.3 12.614343 1.2059e−36  1.00000 N 0.200039 0.129430 KxG HcC 815.5 546.9 3223.8 12.605467 1.3261e−36  1.00000 N 0.252962 0.169638 SxW ChH 89.6 27.5 434.3 12.254000 2.6846e−34  1.00000 N 0.206309 0.063216 VxC EcC 60.4 14.6 326.9 12.283869 2.8734e−34  1.00000 N 0.184766 0.044568 TxD ChH 596.6 380.9 2366.4 12.065391 1.1295e−33  1.00000 N 0.252113 0.160964 QxG HcC 492.4 302.3 1853.5 11.951463 4.6538e−33  1.00000 N 0.265660 0.163098 RxG HcC 600.4 385.3 2430.5 11.946166 4.7458e−33  1.00000 N 0.247027 0.158526 LxP CcH 462.1 275.0 3282.8 11.786533 3.3267e−32  1.00000 N 0.140764 0.083772 PxD ChH 394.7 232.9 1487.4 11.547933 5.7222e−31  1.00000 N 0.265362 0.156556 DxN ChH 418.4 250.6 1597.8 11.545587 5.7935e−31  1.00000 N 0.261860 0.156827 PxS ChH 359.8 206.0 1492.8 11.543336 6.1661e−31  1.00000 N 0.241024 0.137984 NxR ChH 288.4 155.7 1067.1 11.503618 1.0444e−30  1.00000 N 0.270265 0.145939 SxR ChH 317.2 175.7 1335.1 11.460734 1.6564e−30  1.00000 N 0.237585 0.131564 GxC CcH 44.3 9.7 152.7 11.437654 9.0069e−30  1.00000 N 0.290111 0.063838 SxY ChH 163.2 72.1 829.5 11.220669 3.2336e−29  1.00000 N 0.196745 0.086964 QxF EeE 222.0 109.4 1489.4 11.185189 4.2124e−29  1.00000 N 0.149053 0.073447 GxT ChH 279.3 149.2 1676.8 11.158528 5.2645e−29  1.00000 N 0.166567 0.088982 NxD ChH 495.1 313.9 2040.0 11.121331 6.9636e−29  1.00000 N 0.242696 0.153854 NxQ ChH 274.2 149.6 988.7 11.058345 1.6363e−28  1.00000 N 0.277334 0.151307 NxN ChH 250.9 133.3 909.1 11.031095 2.2760e−28  1.00000 N 0.275987 0.146586 QxI EeE 286.5 155.2 2264.8 10.922487 7.1076e−28  1.00000 N 0.126501 0.068519 RxD ChH 290.3 164.7 1023.0 10.679839 9.9908e−27  1.00000 N 0.283773 0.161040 RxG HhC 536.7 352.1 2365.3 10.663828 1.0247e−26  1.00000 N 0.226906 0.148858 RxY EeE 321.4 183.3 2132.7 10.666316 1.1077e−26  1.00000 N 0.150701 0.085960 PxN ChH 192.2 95.7 703.2 10.613987 2.3079e−26  1.00000 N 0.273322 0.136083 GxP CcC 2805.0 2335.4 17106.8 10.456739 7.6737e−26  1.00000 N 0.163970 0.136520 SxT ChH 257.9 141.7 1197.1 10.391203 2.1709e−25  1.00000 N 0.215437 0.118404 QxN EeC 209.1 109.1 732.3 10.376889 2.7159e−25  1.00000 N 0.285539 0.148994 DxY EeE 220.1 114.3 1491.6 10.296246 6.0672e−25  1.00000 N 0.147560 0.076640 SxN ChH 239.0 129.9 996.5 10.263686 8.3511e−25  1.00000 N 0.239839 0.130365 DxG HcC 432.5 277.7 1780.1 10.113180 3.3685e−24  1.00000 N 0.242964 0.155990 YxY EeE 228.8 121.2 2218.0 10.058017 6.7978e−24  1.00000 N 0.103156 0.054624 NxQ CcC 892.6 658.1 4118.3 9.972648 1.2435e−23  1.00000 N 0.216740 0.159798 ExR EeE 515.0 343.7 2444.0 9.970753 1.3711e−23  1.00000 N 0.210720 0.140610 GxT CcE 939.2 694.3 5432.7 9.951870 1.5175e−23  1.00000 N 0.172879 0.127800 GxV CcE 809.8 580.9 6541.4 9.949285 1.5796e−23  1.00000 N 0.123796 0.088803 NxY CcE 207.7 110.3 1062.5 9.790792 1.0127e−22  1.00000 N 0.195482 0.103850 PxY CcC 713.9 507.6 4347.2 9.740513 1.2772e−22  1.00000 N 0.164221 0.116776 AxP HcC 365.8 228.9 1699.7 9.723656 1.6933e−22  1.00000 N 0.215214 0.134695 ExF EeE 256.9 144.6 1850.1 9.723236 1.8348e−22  1.00000 N 0.138857 0.078174 QxG HhC 389.7 248.6 1652.1 9.705388 2.0025e−22  1.00000 N 0.235882 0.150503 TxS ChH 302.5 183.7 1336.5 9.440319 2.7128e−21  1.00000 N 0.226337 0.137430 TxV EeE 635.9 444.3 7269.4 9.382032 4.0803e−21  1.00000 N 0.087476 0.061117 PxA ChH 300.2 182.7 1377.9 9.335371 7.3154e−21  1.00000 N 0.217868 0.132582 SxG HhC 349.5 220.3 1705.1 9.325761 7.7389e−21  1.00000 N 0.204973 0.129216 ExR CeE 196.5 108.0 664.3 9.299003 1.1605e−20  1.00000 N 0.295800 0.162652 QxY EeE 187.6 98.9 1255.4 9.293234 1.2227e−20  1.00000 N 0.149434 0.078777 GxR CcE 762.1 561.9 3614.7 9.192475 2.3756e−20  1.00000 N 0.210834 0.155436 DxR HcC 120.8 57.1 342.9 9.241439 2.3884e−20  1.00000 N 0.352289 0.166413 LxA CcH 231.9 130.5 1826.3 9.214022 2.3961e−20  1.00000 N 0.126978 0.071445 DxG HhC 361.9 232.4 1588.1 9.195611 2.5922e−20  1.00000 N 0.227882 0.146327 CxP ChH 38.6 10.0 195.9 9.318972 2.6851e−20  1.00000 N 0.197039 0.050815 YxY CcE 84.9 33.4 504.5 9.207153 3.8374e−20  1.00000 N 0.168285 0.066298 NxS ChH 286.4 174.8 1258.8 9.101010 6.5075e−20  1.00000 N 0.227518 0.138825 RxP HcC 272.6 165.4 1046.7 9.080465 7.9710e−20  1.00000 N 0.260438 0.158052 DxT ChH 325.9 205.3 1490.9 9.064351 8.8406e−20  1.00000 N 0.218593 0.137700 TxK ChH 363.6 237.5 1518.2 8.909320 3.5284e−19  1.00000 N 0.239494 0.156432 DxN CcC 1643.8 1344.4 8702.1 8.880344 3.8076e−19  1.00000 N 0.188897 0.154491 GxC EcH 23.6 2.0 59.1 15.334095 4.9477e−19  1.00000 B 0.399323 0.034629 WxG CcH 47.8 14.9 153.6 8.967722 5.1676e−19  1.00000 N 0.311198 0.097025 RxF EeE 260.1 154.0 2165.0 8.868217 5.4042e−19  1.00000 N 0.120139 0.071144 NxQ CcE 241.5 143.8 921.8 8.867344 5.6237e−19  1.00000 N 0.261987 0.156009 NxG HcC 306.9 192.6 1423.3 8.859907 5.6640e−19  1.00000 N 0.215626 0.135299 NxG EcC 266.8 161.1 1531.2 8.808720 9.1688e−19  1.00000 N 0.174242 0.105181 DxY ChH 151.5 78.1 697.2 8.818579 9.8907e−19  1.00000 N 0.217298 0.111980 DxR EeE 241.4 143.3 1105.4 8.782154 1.1928e−18  1.00000 N 0.218382 0.129651 GxW CcE 181.9 98.7 1119.5 8.764418 1.4965e−18  1.00000 N 0.162483 0.088199 YxE EeE 316.8 199.4 2122.7 8.730258 1.7640e−18  1.00000 N 0.149244 0.093957 SxN HcC 189.6 106.4 732.9 8.717704 2.2519e−18  1.00000 N 0.258698 0.145238 VxK CcH 158.9 83.0 1054.7 8.679088 3.2923e−18  1.00000 N 0.150659 0.078699 ExR HcC 208.6 122.8 704.9 8.523866 1.1834e−17  1.00000 N 0.295929 0.174169

TABLE 7 In Expected in P-Value P-Value Observed Null Sequence Structure Epitopes Epi In PDB Z-Score Upper Lower Distribution Ratio Probability VGK CCH 77.0 7.3 333.8 26.010341 2.4051e−147 1.00000 N 0.230677 0.021974 GKT CHH 153.4 31.1 637.2 22.460983 3.9337e−111 1.00000 N 0.240741 0.048882 AGK CCH 62.8 6.9 203.7 21.675549 1.1541e−102 1.00000 N 0.308297 0.033809 GKS CHH 109.3 20.3 431.2 20.202696 4.5922e−90  1.00000 N 0.253479 0.047186 SGK CCH 62.0 8.1 285.5 19.164056 1.1096e−80  1.00000 N 0.217163 0.028485 TGK CCH 58.3 9.7 201.6 15.993902 9.7605e−57  1.00000 N 0.289187 0.048116 SCW CHH 23.8 0.1 62.0 65.127700 4.1919e−46  1.00000 B 0.383871 0.002135 KTT HHH 82.7 23.0 432.3 12.788449 3.7526e−37  1.00000 N 0.191302 0.053227 GLG CHH 32.3 5.5 150.3 11.613338 2.1761e−30  1.00000 N 0.214904 0.036728 VAC ECC 35.5 3.0 69.4 19.303678 1.0904e−29  1.00000 B 0.511527 0.042754 ACK CCC 43.1 9.6 105.9 11.302265 4.3157e−29  1.00000 N 0.406988 0.091043 STK CEE 101.6 38.9 261.2 10.906198 1.3949e−27  1.00000 N 0.388974 0.148807 NVA EEC 38.6 8.4 107.2 10.808062 1.0942e−26  1.00000 N 0.360075 0.078810 SWG EEC 39.0 8.5 240.0 10.655127 5.3105e−26  1.00000 N 0.162500 0.035402 LCT CCC 29.6 5.8 90.5 10.256670 5.0074e−24  1.00000 N 0.327072 0.063723 CKN CCC 43.3 11.3 142.4 9.894711 1.0185e−22  1.00000 N 0.304073 0.079616 AAG HCC 163.7 81.2 702.7 9.726602 2.0695e−22  1.00000 N 0.232959 0.115625 TEA CHH 96.0 39.7 292.4 9.607131 8.5115e−22  1.00000 N 0.328317 0.135830 SAA CHH 97.7 40.5 376.8 9.504205 2.2325e−21  1.00000 N 0.259289 0.107580 ACW CHH 7.1 0.0 7.0 66.349669 2.5416e−20  1.00000 B 1.014286 0.001588 TNS HHH 28.8 6.4 113.7 9.149010 1.8584e−19  1.00000 N 0.253298 0.056008 GLP CCC 279.5 169.6 1833.1 8.854745 6.0139e−19  1.00000 N 0.152474 0.092541 NIF CHH 25.6 5.4 79.2 9.005026 8.0205e−19  1.00000 N 0.323232 0.068183 SIP CCC 122.5 58.7 674.0 8.717895 2.5843e−18  1.00000 N 0.181751 0.087074 WCG CCH 28.7 4.0 56.9 12.768736 3.8448e−18  1.00000 B 0.504394 0.070649 FPG CCC 138.7 69.5 857.5 8.665190 3.8961e−18  1.00000 N 0.161749 0.081010 GFT CCH 31.4 8.1 73.3 8.717496 7.2684e−18  1.00000 N 0.428377 0.109906 FTN CHH 29.5 7.6 58.8 8.553956 3.1605e−17  1.00000 N 0.501701 0.128453 QFN CEC 25.0 3.5 41.7 12.091685 4.5918e−17  1.00000 B 0.599520 0.082983 PGP CCC 141.6 73.8 708.1 8.346900 5.8862e−17  1.00000 N 0.199972 0.104156 CSA CCC 35.9 10.0 203.2 8.423091 7.2418e−17  1.00000 N 0.176673 0.049053 NHG CEE 10.8 0.2 15.3 24.175566 8.8421e−17  1.00000 B 0.705882 0.012739 PTW CEE 16.2 1.1 23.2 14.652981 1.4058e−16  1.00000 B 0.698276 0.047995 SRW CHH 21.5 2.1 52.8 13.577010 2.1455e−16  1.00000 B 0.407197 0.040196 MDS ECC 25.5 3.2 83.9 12.774800 2.5660e−16  1.00000 B 0.303933 0.037835 STM CCE 24.9 3.3 57.0 12.327304 3.1613e−16  1.00000 B 0.436842 0.057314 CGP CHH 24.5 3.1 61.6 12.501422 4.2984e−16  1.00000 B 0.397727 0.050135 AGP CCC 129.7 67.0 642.9 8.089518 5.0769e−16  1.00000 N 0.201742 0.104248 GSC CCH 17.4 1.2 46.8 14.920627 7.5249e−16  1.00000 B 0.371795 0.025829 TKV EEE 147.9 80.2 815.1 7.963248 1.3456e−15  1.00000 N 0.181450 0.098379 TVA CHH 40.3 13.0 137.0 7.949197 3.0102e−15  1.00000 N 0.294161 0.095013 QGQ CCC 91.8 43.4 358.4 7.828759 4.6739e−15  1.00000 N 0.256138 0.121185 SVT EEE 97.7 46.7 1097.2 7.630634 2.0807e−14  1.00000 N 0.089045 0.042549 YPS CCC 75.2 33.3 377.0 7.598203 3.0137e−14  1.00000 N 0.199469 0.088388 LSA CCH 54.0 20.6 304.8 7.618303 3.0894e−14  1.00000 N 0.177165 0.067607 TPG CCC 165.0 95.3 927.3 7.542830 3.4767e−14  1.00000 N 0.177936 0.102732 GSC ECH 11.5 0.4 30.6 17.936056 4.0165e−14  1.00000 B 0.375817 0.012703 KVD EEE 140.3 78.3 634.6 7.478628 5.9323e−14  1.00000 N 0.221084 0.123433 VNG ECC 97.3 47.6 641.0 7.485467 6.3078e−14  1.00000 N 0.151794 0.074270 NHA CEE 13.1 0.7 39.4 15.069522 8.1696e−14  1.00000 B 0.332487 0.017519 DAC ECC 11.1 0.4 76.4 17.855983 1.1616e−13  1.00000 B 0.145288 0.004755 PTE CCH 41.7 14.5 177.9 7.447010 1.3352e−13  1.00000 N 0.234401 0.081576 VNT EEE 23.7 5.8 202.1 7.516216 1.3762e−13  1.00000 N 0.117269 0.028818 QRG HCC 49.4 19.2 147.2 7.401983 1.6748e−13  1.00000 N 0.335598 0.130253 DRC CCC 32.2 9.8 128.7 7.444459 1.6904e−13  1.00000 N 0.250194 0.076146 TPN CHH 40.3 14.1 123.0 7.419598 1.6934e−13  1.00000 N 0.327642 0.114566 QSP EEC 55.5 22.0 358.1 7.386743 1.7114e−13  1.00000 N 0.154985 0.061328 NPT CCC 103.0 52.3 577.1 7.347429 1.7329e−13  1.00000 N 0.178479 0.090661 PGA CCC 212.4 132.7 1275.2 7.304192 1.9593e−13  1.00000 N 0.166562 0.104098 TMS CEE 18.0 1.9 61.6 11.976454 2.1832e−13  1.00000 B 0.292208 0.030366 WNI ECC 14.3 1.7 14.6 10.368372 2.5065e−13  1.00000 B 0.979452 0.114714 SLP CCC 173.3 103.4 1051.9 7.242306 3.2273e−13  1.00000 N 0.164750 0.098276 VWG CCC 27.0 7.6 100.7 7.352114 3.9459e−13  1.00000 N 0.268123 0.075068 YAS HHC 21.3 5.1 83.8 7.373798 4.4718e−13  1.00000 N 0.254177 0.061159 ETG HHC 74.9 34.7 331.4 7.207961 5.4644e−13  1.00000 N 0.226011 0.104757 DGR CCC 235.9 153.2 1180.8 7.159780 5.5359e−13  1.00000 N 0.199780 0.129763 PGD CCC 199.2 124.2 1125.9 7.138468 6.6622e−13  1.00000 N 0.176925 0.110285 KYG HHC 97.9 50.3 426.2 7.139373 8.0699e−13  1.00000 N 0.229704 0.118099 PNR HHH 26.3 7.4 104.2 7.227147 9.8791e−13  1.00000 N 0.252399 0.070802 YRG ECC 44.6 16.9 163.1 7.137134 1.2043e−12  1.00000 N 0.273452 0.103338 LPP CCH 51.0 20.2 286.8 7.109054 1.3390e−12  1.00000 N 0.177824 0.070421 ALG HHC 97.2 49.6 629.4 7.045039 1.5728e−12  1.00000 N 0.154433 0.078782 LPP CCC 180.4 110.2 1229.1 7.014972 1.6415e−12  1.00000 N 0.146774 0.089620 VPG CCC 166.4 99.6 1134.4 7.006024 1.7808e−12  1.00000 N 0.146685 0.087813 GLN CCC 129.0 72.3 760.8 7.013456 1.8054e−12  1.00000 N 0.169558 0.095002 DGS CCC 313.8 217.4 1868.1 6.955249 2.2714e−12  1.00000 N 0.167978 0.116375 TQA CHH 28.7 8.8 79.5 7.084686 2.4870e−12  1.00000 N 0.361006 0.111203 LGF HCC 32.9 10.6 200.8 7.063506 2.5027e−12  1.00000 N 0.163845 0.052585 VGS ECC 50.8 20.2 338.6 7.014581 2.6019e−12  1.00000 N 0.150030 0.059706 VGG ECC 71.2 32.4 623.7 6.989302 2.6159e−12  1.00000 N 0.114157 0.052013 DAG HCC 85.4 43.1 354.4 6.866307 5.8013e−12  1.00000 N 0.240971 0.121717 NFQ CCC 43.0 16.4 179.3 6.908802 6.0451e−12  1.00000 N 0.239822 0.091247 PLP CCC 188.1 117.9 1190.8 6.815600 6.5703e−12  1.00000 N 0.157961 0.098979 GVG CCC 153.3 91.0 1178.1 6.798433 7.7111e−12  1.00000 N 0.130125 0.077244 KST HHH 55.7 23.6 352.4 6.836180 8.5034e−12  1.00000 N 0.158059 0.067006 GVC CHH 11.0 0.6 29.2 13.353406 1.0076e−11  1.00000 B 0.376712 0.021150 LNH CCE 18.5 2.6 48.2 10.211731 1.1142e−11  1.00000 B 0.383817 0.053329 FNT ECC 25.2 5.0 90.3 9.300990 1.1273e−11  1.00000 B 0.279070 0.055319 AFG HHC 43.0 16.4 221.9 6.811870 1.1651e−11  1.00000 N 0.193781 0.074044 YDY CCE 24.7 7.0 113.0 6.871379 1.2210e−11  1.00000 N 0.218584 0.062322 EFG HHC 47.2 19.1 189.4 6.788653 1.2971e−11  1.00000 N 0.249208 0.100739 GAD CCC 214.2 138.8 1524.5 6.711627 1.3044e−11  1.00000 N 0.140505 0.091053 PGY CCC 82.9 41.6 425.5 6.738554 1.3978e−11  1.00000 N 0.194830 0.097795 VSG ECC 37.7 13.5 238.1 6.793587 1.4324e−11  1.00000 N 0.158337 0.056600 VPS CHH 23.5 6.7 71.3 6.843087 1.5709e−11  1.00000 N 0.329593 0.093573 NTK CEE 60.7 27.9 192.9 6.723444 1.7833e−11  1.00000 N 0.314671 0.144478 KEG HHC 69.4 33.3 254.1 6.699047 1.9722e−11  1.00000 N 0.273121 0.131224 ERG HCC 94.3 50.4 359.7 6.658952 2.3048e−11  1.00000 N 0.262163 0.140245 TGN CCH 20.5 3.8 35.3 8.996500 2.3578e−11  1.00000 B 0.580737 0.108948

TABLE 8 In Expected in P-Value P-Value Observed Null Sequence Structure Epitopes Epi In PDB Z-Score Upper Lower Distribution Ratio Probability ExxR HhhH 4348.2 2217.2 15346.0 48.929948 0.0000e+00  1.00000 N 0.283344 0.144479 DxxR HhhH 1950.8 1065.5 7576.4 29.254482 3.1941e−188 1.00000 N 0.257484 0.140641 AxxR HhhH 1961.9 1175.2 11570.1 24.209128 1.2946e−129 1.00000 N 0.169566 0.101576 QxxR HhhH 1231.2 658.8 5042.5 23.915382 1.7473e−126 1.00000 N 0.244165 0.130659 RxxE HhhH 2176.8 1363.9 9113.5 23.870272 4.4302e−126 1.00000 N 0.238854 0.149656 SxxE ChhH 1232.3 662.1 5215.8 23.715081 2.0648e−124 1.00000 N 0.236263 0.126945 TxxE ChhH 1201.2 669.0 5025.4 22.099248 2.5443e−108 1.00000 N 0.239026 0.133125 RxxR HhhH 1439.9 849.7 5869.7 21.892063 2.3219e−106 1.00000 N 0.245311 0.144767 NxxR HhhH 887.4 483.2 3933.1 19.632154 6.6235e−86  1.00000 N 0.225624 0.122860 ExxL HhhH 2067.7 1372.8 16331.3 19.596830 1.0853e−85  1.00000 N 0.126610 0.084059 ExxE HhhH 2778.6 2009.6 13291.7 18.618528 1.4251e−77  1.00000 N 0.209048 0.151195 RxxQ HhhH 1120.7 683.5 5021.1 17.993739 1.5808e−72  1.00000 N 0.223198 0.136120 AxxA HhhH 1938.9 1310.0 22725.8 17.898378 7.8366e−72  1.00000 N 0.085317 0.057645 LxxQ HhhH 1044.9 618.7 8365.8 17.803559 4.8141e−71  1.00000 N 0.124901 0.073960 TxxQ ChhH 610.7 320.4 2537.9 17.349010 1.6872e−67  1.00000 N 0.240632 0.126252 LxxE HhhH 1464.3 953.5 12363.8 17.217744 1.3074e−66  1.00000 N 0.118434 0.077123 SxxR HhhH 897.4 526.5 4584.1 17.180436 2.7728e−66  1.00000 N 0.195764 0.114856 PxxR HhhH 724.7 403.3 3049.0 17.179959 2.9726e−66  1.00000 N 0.237684 0.132276 ExxK HhhH 3386.2 2586.3 16930.7 17.087679 1.1008e−65  1.00000 N 0.200004 0.152759 ExxG HhhC 927.7 556.2 3737.1 17.076826 1.6364e−65  1.00000 N 0.248241 0.148819 NxxE ChhH 661.0 364.0 2655.9 16.758653 3.9327e−63  1.00000 N 0.248880 0.137048 AxxG HhhC 719.2 401.9 3735.5 16.753239 4.1779e−63  1.00000 N 0.192531 0.107594 ExxH HhhH 621.9 333.5 3030.1 16.736834 5.7488e−63  1.00000 N 0.205241 0.110077 ExxA HhhH 2290.7 1653.8 15597.0 16.562861 8.0240e−62  1.00000 N 0.146868 0.106036 QxxE HhhH 1402.9 938.5 6562.3 16.375826 1.9012e−60  1.00000 N 0.213782 0.143012 AxxQ HhhH 1213.0 780.1 7792.0 16.340013 3.4909e−60  1.00000 N 0.155672 0.100112 QxxQ HhhH 966.0 596.4 4465.5 16.256537 1.4369e−59  1.00000 N 0.216325 0.133567 SxxQ ChhH 506.0 259.3 2528.0 16.170844 6.8893e−59  1.00000 N 0.200158 0.102577 QxxA HhhH 1224.8 792.5 8547.3 16.121839 1.2114e−58  1.00000 N 0.143297 0.092719 AxxE HhhH 1984.0 1414.1 13871.3 15.991423 9.1835e−58  1.00000 N 0.143029 0.101946 ExxN HhhH 1108.5 713.4 5126.3 15.942068 2.2333e−57  1.00000 N 0.216238 0.139170 QxxL HhhH 1100.1 695.9 9726.7 15.900088 4.3300e−57  1.00000 N 0.113101 0.071549 QxxK HhhH 1225.8 809.9 5705.9 15.775674 3.0884e−56  1.00000 N 0.214830 0.141944 KxxG HhhC 867.2 534.5 3433.8 15.658935 2.0892e−55  1.00000 N 0.252548 0.155669 NxxQ ChhH 332.0 152.1 1273.8 15.544051 1.7117e−54  1.00000 N 0.260637 0.119410 SxxQ HhhH 668.9 384.6 3261.9 15.434403 7.3145e−54  1.00000 N 0.205065 0.117911 RxxG HhhC 641.9 369.4 2583.0 15.313256 4.8017e−53  1.00000 N 0.248509 0.143024 SxxD ChhH 740.5 443.0 3728.2 15.055046 2.3442e−51  1.00000 N 0.198621 0.118834 DxxE HhhH 1237.9 835.4 5826.5 15.045687 2.4433e−51  1.00000 N 0.212460 0.143381 ExxQ HhhH 1562.3 1108.4 7657.2 14.743542 2.1528e−49  1.00000 N 0.204030 0.144748 GxxT ChhH 295.6 132.8 1720.0 14.702270 6.0666e−49  1.00000 N 0.171860 0.077226 YxxE HhhH 584.6 335.1 3516.7 14.330678 1.0637e−46  1.00000 N 0.166235 0.095283 NxxN HhhH 471.7 257.7 2067.4 14.251900 3.5119e−46  1.00000 N 0.228161 0.124630 ExxR HhhC 380.1 197.9 1322.8 14.041511 7.4744e−45  1.00000 N 0.287345 0.149630 QxxG HhhC 411.9 219.5 1555.2 14.009672 1.1350e−44  1.00000 N 0.264853 0.141160 TxxR HhhH 765.0 482.3 4295.0 13.660714 1.2139e−42  1.00000 N 0.178114 0.112300 DxxE ChhH 635.3 386.1 2788.7 13.662147 1.2445e−42  1.00000 N 0.227812 0.138458 YxxQ HhhH 398.5 209.7 2527.7 13.617674 2.5739e−42  1.00000 N 0.157653 0.082949 QxxN HhhH 542.7 316.8 2555.0 13.561238 5.1153e−42  1.00000 N 0.212407 0.123988 DxxG HhhC 433.3 241.9 1739.4 13.261160 3.0841e−40  1.00000 N 0.249109 0.139082 WxxE HhhH 321.8 161.2 1855.3 13.242353 4.3211e−40  1.00000 N 0.173449 0.086864 ExxD HhhH 1269.7 909.8 6134.4 12.929975 1.9255e−38  1.00000 N 0.206980 0.148308 HxxR HhhH 430.4 241.7 2107.3 12.903646 3.3433e−38  1.00000 N 0.204242 0.114677 DxxL HhhH 1010.9 687.7 8629.3 12.846314 5.8301e−38  1.00000 N 0.117147 0.079696 ExxG HhcC 744.6 484.9 3281.4 12.775335 1.5440e−37  1.00000 N 0.226915 0.147772 ExxS HhhH 1097.9 768.3 6163.8 12.711229 3.2768e−37  1.00000 N 0.178121 0.124641 QxxI HhhH 566.2 340.5 4971.5 12.671523 6.0800e−37  1.00000 N 0.113889 0.068494 DxxA ChhH 593.4 365.5 3282.0 12.648212 8.1426e−37  1.00000 N 0.180804 0.111354 SxxG HhhC 347.9 186.1 1537.7 12.646200 9.6469e−37  1.00000 N 0.226247 0.121053 AxxD HhhH 1046.4 726.1 6872.9 12.566935 2.0561e−36  1.00000 N 0.152250 0.105654 HxxN HhhH 260.9 127.1 1176.7 12.560981 3.1284e−36  1.00000 N 0.221722 0.108046 DxxQ HhhH 723.6 471.1 3555.4 12.487682 5.9445e−36  1.00000 N 0.203521 0.132515 KxxR HhhH 1092.2 773.5 5096.1 12.440642 1.0036e−35  1.00000 N 0.214321 0.151790 KxxE HhhH 2359.1 1866.8 12050.7 12.393165 1.6647e−35  1.00000 N 0.195765 0.154916 ExxY HhhH 594.3 368.6 4092.2 12.321576 4.8612e−35  1.00000 N 0.145228 0.090082 DxxS ChhH 389.9 219.1 1996.9 12.233933 1.5902e−34  1.00000 N 0.195253 0.109696 RxxE ChhH 293.5 153.3 1085.3 12.219943 2.0770e−34  1.00000 N 0.270432 0.141246 NxxA HhhH 615.2 385.8 4642.0 12.194745 2.2966e−34  1.00000 N 0.132529 0.083118 RxxG HhcC 659.6 428.8 2824.2 12.104920 6.8433e−34  1.00000 N 0.233553 0.151816 NxxD ChhH 392.2 223.3 1771.2 12.091210 9.0805e−34  1.00000 N 0.221432 0.126069 DxxQ ChhH 408.5 236.2 1714.9 12.072696 1.1263e−33  1.00000 N 0.238206 0.137738 NxxL ChhH 281.7 142.8 1993.4 12.058417 1.4819e−33  1.00000 N 0.141316 0.071657 HxxE HhhH 473.2 283.5 2266.1 12.043282 1.5453e−33  1.00000 N 0.208817 0.125115 GxxE ChhH 439.0 257.5 2293.0 12.008640 2.3858e−33  1.00000 N 0.191452 0.112279 NxxQ HhhH 424.5 248.0 2082.1 11.945249 5.1603e−33  1.00000 N 0.203881 0.119090 PxxQ ChhH 241.0 119.4 891.4 11.960056 5.1935e−33  1.00000 N 0.270361 0.133930 DxxI HhhH 616.4 390.7 5172.8 11.873778 1.1089e−32  1.00000 N 0.119162 0.075536 DxxN HhhH 709.7 470.7 3574.6 11.821688 2.0234e−32  1.00000 N 0.198540 0.131680 PxxQ HhhH 457.1 275.6 2183.2 11.694718 9.9071e−32  1.00000 N 0.209372 0.126244 AxxS HhhH 758.2 505.5 6977.1 11.670720 1.1797e−31  1.00000 N 0.108670 0.072450 PxxE ChhH 403.9 238.4 1641.8 11.591112 3.4386e−31  1.00000 N 0.246010 0.145223 LxxR HhhH 1020.1 722.6 9691.9 11.504616 7.8213e−31  1.00000 N 0.105253 0.074557 DxxD ChhH 374.5 215.7 1824.1 11.518567 8.0950e−31  1.00000 N 0.205307 0.118228 NxxN ChhH 243.7 123.8 1030.3 11.485674 1.3538e−30  1.00000 N 0.236533 0.120178 DxxR ChhH 424.4 255.7 1831.5 11.375735 4.0622e−30  1.00000 N 0.231723 0.139600 NxxA ChhH 312.9 171.5 1945.5 11.304387 9.8336e−30  1.00000 N 0.160833 0.088165 YxxR HhhH 419.1 249.3 2896.8 11.250980 1.6663e−29  1.00000 N 0.144677 0.086053 DxxL ChhH 415.6 247.0 2867.7 11.221422 2.3305e−29  1.00000 N 0.144925 0.086134 QxxY HhhH 320.8 177.7 2179.5 11.200574 3.1483e−29  1.00000 N 0.147190 0.081535 DxxT ChhH 458.9 282.2 2519.2 11.161309 4.4957e−29  1.00000 N 0.182161 0.112025 CxxC HhhH 91.2 31.4 345.5 11.183314 7.0327e−29  1.00000 N 0.263965 0.090959 PxxL HhhH 608.9 395.6 6143.7 11.089911 9.3855e−29  1.00000 N 0.099110 0.064384 DxxY HhhH 368.3 213.9 2333.5 11.075011 1.2369e−28  1.00000 N 0.157832 0.091673 KxxG HhcC 745.1 514.8 3321.5 11.041005 1.5816e−28  1.00000 N 0.224326 0.154995 RxxD HhhH 732.4 503.2 3530.9 11.036073 1.6724e−28  1.00000 N 0.207426 0.142503 RxxG EecC 324.0 184.1 1428.3 11.048350 1.7317e−28  1.00000 N 0.226843 0.128887 GxxS ChhH 183.5 85.6 1241.1 10.968621 5.0167e−28  1.00000 N 0.147853 0.068961 DxxA HhhH 1133.7 834.4 8331.6 10.924825 5.3609e−28  1.00000 N 0.136072 0.100143 RxxQ ChhH 123.0 50.4 388.2 10.969534 6.1545e−28  1.00000 N 0.316847 0.129758

TABLE 9 In Expected P-Value P-Value Observed Null Sequence Structure Epitopes in Epi In PDB Z-Score Upper Lower Distribution Ratio Probability GxGK CcCH 167.7 26.9 711.5 27.705426 4.5759e−168 1.00000 N 0.235699 0.037747 VxKS CcHH 52.9 6.6 219.9 18.362884 4.9087e−74 1.00000 N 0.240564 0.029847 GxTT ChHH 83.7 17.2 346.9 16.454208 2.9941e−60 1.00000 N 0.241280 0.049554 GxCW CcHH 29.6 0.4 45.0 46.718591 4.9102e−49 1.00000 B 0.657778 0.008761 VxCK EcCC 42.0 3.1 60.9 22.843225 2.8454e−40 1.00000 B 0.689655 0.050241 GxCW EcHH 23.1 0.3 37.8 42.803527 1.7396e−39 1.00000 B 0.611111 0.007573 AxKT CcHH 36.8 2.4 104.5 22.244125 1.2660e−32 1.00000 B 0.352153 0.023376 CxNG CcCC 44.4 9.3 177.5 11.796465 1.4799e−31 1.00000 N 0.250141 0.052558 SxAE ChHH 122.9 48.4 589.8 11.168674 6.7314e−29 1.00000 N 0.208376 0.082117 NxGK CcCH 34.8 3.3 86.9 17.596286 3.5249e−26 1.00000 B 0.400460 0.038281 TxKT CcHH 39.5 4.3 154.6 17.143559 3.7891e−26 1.00000 B 0.255498 0.028007 NxAC EeCC 27.0 2.0 50.4 18.153492 6.3631e−25 1.00000 B 0.535714 0.039237 TxAE ChHH 127.2 56.2 609.9 9.932803 3.0165e−23 1.00000 N 0.208559 0.092199 FxNS ChHH 27.7 2.3 55.4 16.958631 3.7819e−23 1.00000 B 0.500000 0.042157 GxTN CcHH 32.2 7.1 72.4 9.871338 1.9381e−22 1.00000 N 0.444751 0.098713 QxGK CcCH 29.0 3.4 42.7 14.374481 3.4874e−22 1.00000 B 0.679157 0.080540 GxST ChHH 55.4 16.7 309.3 9.733730 3.7002e−22 1.00000 N 0.179114 0.054010 TxAQ ChHH 65.5 22.0 303.2 9.611531 1.0400e−21 1.00000 N 0.216029 0.072705 DxEG HhHC 38.2 9.8 91.3 9.586215 2.3137e−21 1.00000 N 0.418401 0.107564 SxEE ChHH 251.6 144.3 1525.5 9.392189 4.4475e−21 1.00000 N 0.164930 0.094565 SxKT CcHH 30.5 3.1 137.0 15.606960 5.0423e−21 1.00000 B 0.222628 0.022952 NxRG CeCC 26.1 5.5 50.1 9.307237 5.3638e−20 1.00000 N 0.520958 0.109822 KxDK EeEE 103.4 45.3 400.6 9.155613 5.5926e−20 1.00000 N 0.258113 0.113187 KxTG HhHC 76.9 30.0 329.0 8.978773 3.2532e−19 1.00000 N 0.233739 0.091216 SxTK HcEE 87.3 36.5 320.2 8.926379 4.8515e−19 1.00000 N 0.272642 0.114065 FxGH CcCH 12.2 0.2 23.1 25.026094 1.0525e−18 1.00000 B 0.528139 0.010002 GxTS ChHH 29.2 6.7 121.4 8.949970 1.0560e−18 1.00000 N 0.240527 0.055132 CxAG CcCC 36.3 9.5 225.9 8.891002 1.3288e−18 1.00000 N 0.160691 0.042014 GxGR CcCH 30.7 7.3 148.4 8.862278 2.1091e−18 1.00000 N 0.206873 0.049330 TxVD EeEE 116.5 54.9 674.4 8.681155 3.6299e−18 1.00000 N 0.172746 0.081358 PxWN CeEC 13.5 0.6 14.0 17.598010 4.8699e−18 1.00000 B 0.964286 0.040219 AxGL HcCC 79.5 32.1 539.5 8.617327 7.5507e−18 1.00000 N 0.147359 0.059556 SxYQ ChHH 24.4 5.2 78.1 8.742181 8.3452e−18 1.00000 N 0.312420 0.066298 RxNG EeCC 51.7 17.5 171.1 8.620737 9.9272e−18 1.00000 N 0.302162 0.102376 QxPN HcHH 26.8 6.3 56.5 8.705318 1.0034e−17 1.00000 N 0.474336 0.110806 GxLA CcCE 25.1 2.7 98.2 13.717935 2.3659e−17 1.00000 B 0.255601 0.027844 TxNR ChHH 29.0 4.4 76.1 12.133203 6.1385e−17 1.00000 B 0.381078 0.057443 TxEE ChHH 243.4 147.4 1546.4 8.314461 6.6330e−17 1.00000 N 0.157398 0.095312 NxAL ChHH 30.5 7.7 168.3 8.377216 1.2719e−16 1.00000 N 0.181224 0.045980 TxTG CcCC 114.1 55.4 731.8 8.204551 2.0652e−16 1.00000 N 0.155917 0.075694 SxKS CcHH 27.2 6.5 176.6 8.271558 3.4649e−16 1.00000 N 0.154020 0.036814 WxGP CcHH 27.2 4.5 50.2 11.245730 5.9545e−16 1.00000 B 0.541833 0.089269 GxSS ChHH 25.9 6.1 149.4 8.136343 1.0923e−15 1.00000 N 0.173360 0.041144 SxAD ChHH 93.1 42.9 534.3 7.998864 1.1948e−15 1.00000 N 0.174247 0.080239 PxNV ChHH 25.4 6.1 97.5 8.121634 1.2689e−15 1.00000 N 0.260513 0.062064 QxTG HhHC 36.3 10.8 146.5 8.059476 1.3787e−15 1.00000 N 0.247782 0.073749 NxCN CcCC 27.4 6.9 110.2 8.055912 1.9302e−15 1.00000 N 0.248639 0.062659 GxGL CcCH 28.6 7.4 180.7 7.990101 3.0473e−15 1.00000 N 0.158273 0.040752 QxNT CeCC 22.2 3.4 31.0 10.894909 3.4768e−15 1.00000 B 0.716129 0.108225 GxGF EcCE 16.8 1.2 40.5 14.399043 3.7361e−15 1.00000 B 0.414815 0.029841 TxEQ ChHH 131.0 69.3 722.9 7.799428 5.1196e−15 1.00000 N 0.181215 0.095827 ExLG HhHC 117.4 59.7 783.8 7.773841 6.4656e−15 1.00000 N 0.149783 0.076139 MxIF CcHH 24.6 3.6 56.8 11.457873 6.4773e−15 1.00000 B 0.433099 0.063193 LxHA CcEE 11.8 0.4 33.3 19.335145 7.4581e−15 1.00000 B 0.354354 0.010636 MxLC EeCC 9.0 0.2 15.1 22.286623 8.2126e−15 1.00000 B 0.596026 0.010533 SxLP HhCC 41.8 13.8 235.1 7.791006 9.8874e−15 1.00000 N 0.177797 0.058524 SxKV CeEE 74.8 32.8 361.7 7.687742 1.5248e−14 1.00000 N 0.206801 0.090709 YxTM CcCE 19.6 2.1 43.7 12.252047 2.0037e−14 1.00000 B 0.448513 0.048882 DxCQ EcCC 15.9 1.0 105.6 14.568386 3.6015e−14 1.00000 B 0.150568 0.009939 LxDW EcCC 10.1 0.3 23.0 18.614550 6.7635e−14 1.00000 B 0.439130 0.012246 RxGL HhCC 42.9 15.0 220.2 7.477473 1.0395e−13 1.00000 N 0.194823 0.067983 SxEQ ChHH 106.6 54.0 926.8 7.379054 1.3464e−13 1.00000 N 0.115019 0.058249 VxKT CcHH 25.3 3.9 163.9 10.987962 1.5771e−13 1.00000 B 0.154362 0.023729 YxSG HhCC 28.3 8.0 122.7 7.457246 1.7456e−13 1.00000 N 0.230644 0.064853 NxGY EcCC 21.7 3.1 58.1 10.941103 2.7368e−13 1.00000 B 0.373494 0.052720 GxFM CcCH 10.0 0.5 10.7 13.642568 3.2977e−13 1.00000 B 0.934579 0.047496 SxMS CcEE 14.9 1.1 51.5 13.353266 3.9684e−13 1.00000 B 0.289320 0.021211 YxGD EeCC 25.4 6.8 119.1 7.343589 4.4620e−13 1.00000 N 0.213266 0.057113 NxLP HhCC 31.4 9.5 153.2 7.304107 4.7698e−13 1.00000 N 0.204961 0.062314 NxED ChHH 68.8 30.8 317.4 7.204843 5.8007e−13 1.00000 N 0.216761 0.097047 SxDE ChHH 97.5 49.7 519.2 7.121477 9.1460e−13 1.00000 N 0.187789 0.095803 YxGS EcCC 36.1 12.1 183.1 7.135684 1.4043e−12 1.00000 N 0.197160 0.066120 RxHG HhHC 25.6 7.2 82.9 7.166051 1.5713e−12 1.00000 N 0.308806 0.086994 AxGK CcCH 26.4 7.4 177.4 7.117663 2.1019e−12 1.00000 N 0.148816 0.041830 SxSE ChHH 61.7 26.9 315.1 7.001886 2.5790e−12 1.00000 N 0.195811 0.085508 DxVT EeEE 24.9 6.8 171.0 7.088115 2.7435e−12 1.00000 N 0.145614 0.039734 PxKC CcCH 12.3 1.3 12.5 10.266594 3.6601e−12 1.00000 B 0.984000 0.102657 KxLG HhHC 102.4 53.8 672.1 6.913764 3.8864e−12 1.00000 N 0.152358 0.080006 RxSE EeCC 29.1 8.9 141.3 7.008188 4.1037e−12 1.00000 N 0.205945 0.062855 TxNI EeCC 15.3 1.7 25.9 10.648995 6.3319e−12 1.00000 B 0.590734 0.067123 AxGF HcCC 33.5 11.1 222.8 6.917099 6.7617e−12 1.00000 N 0.150359 0.049674 PxSQ ChHH 31.3 10.2 111.0 6.920163 7.0916e−12 1.00000 N 0.281982 0.092073 ExLP HhCC 42.2 15.8 295.8 6.839588 9.7186e−12 1.00000 N 0.142664 0.053319 KxHG HhCC 42.9 16.6 163.8 6.820623 1.1077e−11 1.00000 N 0.261905 0.101187 GxGR CcHH 20.4 3.0 109.2 10.222967 1.2503e−11 1.00000 B 0.186813 0.027325 VxHG CcEE 7.8 0.1 17.8 19.977321 1.5310e−11 1.00000 B 0.438202 0.008312 DxAS ChHH 45.9 18.2 275.4 6.736084 1.8618e−11 1.00000 N 0.166667 0.065934 ExFG HhHC 57.0 24.7 365.9 6.717061 1.8836e−11 1.00000 N 0.155780 0.067613 ExSG HhHC 34.0 11.8 154.5 6.751139 2.0640e−11 1.00000 N 0.220065 0.076071 RxTG HhHC 45.1 17.9 213.7 6.711082 2.2341e−11 1.00000 N 0.211044 0.083822 ExTG HhHC 52.2 22.0 309.4 6.677412 2.5699e−11 1.00000 N 0.168714 0.071133 NxAQ ChHH 32.7 11.2 137.8 6.713106 2.7429e−11 1.00000 N 0.237300 0.081146 SxQE ChHH 54.8 23.8 271.3 6.647848 3.0642e−11 1.00000 N 0.201990 0.087780 CxSC CcCH 7.0 0.1 36.8 20.082842 3.1318e−11 1.00000 B 0.190217 0.003201 FxTN EcCC 19.5 3.0 66.8 9.782338 3.5580e−11 1.00000 B 0.291916 0.044669 TxNG EeCC 49.7 20.7 275.2 6.622482 3.8018e−11 1.00000 N 0.180596 0.075273 PxDQ ChHH 43.8 17.5 180.6 6.602266 4.6907e−11 1.00000 N 0.242525 0.097075 QxVI CcCC 24.5 7.2 107.7 6.666417 4.7835e−11 1.00000 N 0.227484 0.066942 ExGG EeCC 45.4 18.2 306.7 6.559515 6.0218e−11 1.00000 N 0.148027 0.059455

TABLE 10 In Expected P-Value P-Value Observed Null Sequence Structure Epitopes in Epi In PDB Z-Score Upper Lower Distribution Ratio Probability GKxT CHhH 137.0 18.6 556.5 27.928770 1.6042e−170 1.00000 N 0.246181 0.033414 GKxS CHhH 56.2 5.0 184.9 23.104150 3.8172e−116 1.00000 N 0.303948 0.027261 TGxT CChH 69.6 9.6 241.3 19.717926 1.9252e−85 1.00000 N 0.288438 0.039924 VGxS CChH 50.5 6.3 209.2 17.879802 3.1232e−70 1.00000 N 0.241396 0.030118 NKxD ECcC 74.1 12.7 233.0 17.719652 1.9024e−69 1.00000 N 0.318026 0.054503 GSxK CCcH 46.5 6.2 194.2 16.436360 1.4881e−59 1.00000 N 0.239444 0.031966 GVxK CCcH 55.3 9.0 278.3 15.716574 8.3454e−55 1.00000 N 0.198706 0.032256 CKxG CCcC 51.5 11.1 173.9 12.558736 1.2519e−35 1.00000 N 0.296147 0.063651 GTxK CCcH 35.3 5.8 178.9 12.475785 7.0287e−35 1.00000 N 0.197317 0.032332 GFxN CChH 31.2 5.6 56.9 11.416464 2.1905e−29 1.00000 N 0.548330 0.098116 WCxP CChH 33.3 2.6 62.5 19.373109 4.2055e−29 1.00000 B 0.532800 0.041887 FTxS CHhH 27.7 2.2 52.5 17.490092 6.0171e−24 1.00000 B 0.527619 0.042219 NVxC EEcC 26.5 1.9 52.2 17.922628 8.5115e−24 1.00000 B 0.507663 0.037341 VAxK ECcC 33.3 7.2 90.1 10.147731 1.2188e−23 1.00000 N 0.369589 0.079833 SGxT CChH 34.7 7.7 211.7 9.940448 8.6460e−23 1.00000 N 0.163911 0.036237 AGxT CChH 36.4 4.4 143.7 15.434531 9.7685e−23 1.00000 B 0.253305 0.030811 GGxM CCcH 30.4 3.0 94.6 16.207156 2.5281e−22 1.00000 B 0.321353 0.031282 SGxS CChH 27.3 5.3 185.2 9.755693 7.5361e−22 1.00000 N 0.147408 0.028376 ERxG HHcC 76.1 28.0 265.7 9.603856 1.0100e−21 1.00000 N 0.286413 0.105454 DSxE CChH 66.0 22.6 239.7 9.582583 1.3711e−21 1.00000 N 0.275344 0.094387 RExG HHhC 92.3 37.7 353.8 9.418390 5.1848e−21 1.00000 N 0.260882 0.106451 DSxT EEeE 32.3 7.5 89.0 9.470465 8.5068e−21 1.00000 N 0.362921 0.084184 QFxT CEcC 21.3 1.6 29.7 16.061616 9.1250e−21 1.00000 B 0.717172 0.053568 GAxK CCcH 35.5 5.0 135.7 13.978985 2.4411e−20 1.00000 B 0.261606 0.036517 VGxT CChH 29.1 6.4 179.3 9.116224 2.4335e−19 1.00000 N 0.162298 0.035804 NQxP HHcH 28.5 6.6 58.0 9.017809 6.1701e−19 1.00000 N 0.491379 0.114435 TKxD EEeE 103.5 46.7 416.7 8.823218 1.1095e−18 1.00000 N 0.248380 0.112045 QAxG HHcC 58.1 20.4 220.9 8.766703 2.5643e−18 1.00000 N 0.263015 0.092292 KVxK EEeE 129.0 63.4 665.5 8.662445 4.1119e−18 1.00000 N 0.193839 0.095260 IDxS ECcE 41.4 12.0 221.9 8.712627 5.4346e−18 1.00000 N 0.186571 0.054175 STxV CEeE 79.7 33.6 368.4 8.334380 8.3322e−17 1.00000 N 0.216341 0.091281 FYxM CCcE 1.0 0.1 1.0 3.846944 1.0400e−16 1.00000 B 1.000000 0.063295 NIxM HCcC 1.0 0.0 1.0 4.415241 1.0561e−16 1.00000 B 1.000000 0.048794 PTxN CEeC 15.5 1.1 17.1 14.132918 1.0977e−16 1.00000 B 0.906433 0.064841 NKxG HHhC 32.2 8.7 87.3 8.377682 1.2095e−16 1.00000 N 0.368843 0.099933 NKxD EChH 24.2 5.3 121.7 8.342068 2.3144e−16 1.00000 N 0.198850 0.043910 YAxG HHcC 30.2 7.8 110.3 8.294939 2.5405e−16 1.00000 N 0.273799 0.070980 YSxM CCcE 23.7 2.8 61.6 12.840494 3.5944e−16 1.00000 B 0.384740 0.045127 ACxN CCcC 23.9 5.4 105.8 8.125941 1.3307e−15 1.00000 N 0.225898 0.051421 RRxG HHhC 58.0 22.3 215.4 7.997367 1.5668e−15 1.00000 N 0.269266 0.103372 FPxH CCcH 12.5 0.5 22.2 17.814824 2.2978e−15 1.00000 B 0.563063 0.020995 VSxG EEeC 28.5 7.3 361.1 7.916574 5.3875e−15 1.00000 N 0.078926 0.020248 RAxG HHcC 86.6 40.4 412.0 7.653312 1.8592e−14 1.00000 N 0.210194 0.098060 KDxG HHhC 61.6 25.2 236.0 7.660531 2.0910e−14 1.00000 N 0.261017 0.106924 SSxK HCeE 57.9 23.2 198.2 7.653307 2.2980e−14 1.00000 N 0.292129 0.117242 RRxG HHcC 56.3 22.3 211.9 7.619259 3.0185e−14 1.00000 N 0.265691 0.105141 KKxG HHhC 87.7 41.5 381.6 7.588969 3.0299e−14 1.00000 N 0.229822 0.108834 GSxW EChH 11.0 0.3 38.1 18.116766 3.7547e−14 1.00000 B 0.288714 0.009156 GLxP CCcH 48.9 17.8 319.3 7.570949 4.6990e−14 1.00000 N 0.153148 0.055852 KGxG CChH 21.6 5.0 71.7 7.659772 5.4871e−14 1.00000 N 0.301255 0.070178 KQxT CEeE 26.1 4.9 50.9 10.135942 5.6397e−14 1.00000 B 0.512770 0.095404 ARxP HHcC 39.6 13.4 140.5 7.511607 8.6527e−14 1.00000 N 0.281851 0.095553 ETxS ECcC 29.2 8.4 99.1 7.526295 1.0238e−13 1.00000 N 0.294652 0.084439 DKxG HHhC 59.5 24.9 228.9 7.356353 2.0816e−13 1.00000 N 0.259939 0.108634 KPxY CCcC 42.7 15.2 188.2 7.350314 2.6651e−13 1.00000 N 0.226886 0.080837 QTxK CCcH 17.8 2.2 26.3 10.850825 3.1717e−13 1.00000 B 0.676806 0.085419 RSxG HHcC 54.3 22.0 224.4 7.250022 4.7424e−13 1.00000 N 0.241979 0.098051 KMxF CCcC 23.1 6.0 83.2 7.217699 1.2237e−12 1.00000 N 0.277644 0.072479 RKxG HHhC 59.6 25.6 254.0 7.098040 1.3380e−12 1.00000 N 0.234646 0.100650 EExG HHhC 98.4 50.6 520.0 7.065914 1.3554e−12 1.00000 N 0.189231 0.097369 AAxG HHhC 75.4 35.0 497.1 7.073599 1.4144e−12 1.00000 N 0.151680 0.070477 LSxE CChH 112.6 60.1 832.4 7.032831 1.6319e−12 1.00000 N 0.135272 0.072187 KAxG HHcC 86.7 43.1 434.8 7.007685 2.1431e−12 1.00000 N 0.199402 0.099021 MNxF CChH 25.2 4.9 62.4 9.506941 2.2013e−12 1.00000 B 0.403846 0.079074 LTxW ECcC 10.1 0.4 19.7 15.073737 2.2502e−12 1.00000 B 0.512690 0.021385 NPxE CCcH 23.8 6.4 92.8 7.124827 2.2574e−12 1.00000 N 0.256466 0.069004 WLxV EEcC 11.0 0.8 12.3 11.619322 2.4161e−12 1.00000 B 0.894309 0.066848 GVxF CEeE 20.8 5.1 180.9 7.100474 3.1004e−12 1.00000 N 0.114981 0.027956 SAxG HHhC 37.8 13.3 158.5 7.005915 3.3764e−12 1.00000 N 0.238486 0.084068 CGxC CEcH 10.3 0.4 33.8 15.665276 3.9680e−12 1.00000 B 0.304734 0.011950 GSxW CChH 13.8 1.0 55.6 12.942109 4.0102e−12 1.00000 B 0.248201 0.017924 KNxA EEeC 20.4 5.2 50.6 7.054783 4.4588e−12 1.00000 N 0.403162 0.102437 EAxG HHcC 82.7 40.7 436.1 6.903283 4.5200e−12 1.00000 N 0.189635 0.093429 GKxA CHhH 32.0 10.2 237.0 6.946622 5.7267e−12 1.00000 N 0.135021 0.043241 QKxG HHhC 50.3 20.7 190.7 6.898030 5.9432e−12 1.00000 N 0.263765 0.108445 FMxQ CEeE 13.1 0.9 62.3 12.683560 7.8246e−12 1.00000 B 0.210273 0.014993 LAxG HHcC 73.6 34.7 547.8 6.815209 8.6277e−12 1.00000 N 0.134356 0.063400 FNxN ECcC 20.7 5.2 107.5 6.950636 8.7080e−12 1.00000 N 0.192558 0.048520 TQxG HHcC 23.6 6.7 73.0 6.857650 1.4179e−11 1.00000 N 0.323288 0.091676 TWxI EEcC 12.3 1.2 15.1 10.555052 1.8885e−11 1.00000 B 0.814570 0.079552 WGxG ECcC 39.1 14.1 669.1 6.742288 1.9532e−11 1.00000 N 0.058437 0.021034 DRxG HHhC 37.3 13.7 145.5 6.710008 2.5502e−11 1.00000 N 0.256357 0.094011 GDxT CCcE 34.9 12.3 154.9 6.715037 2.5763e−11 1.00000 N 0.225307 0.079419 PFxA CCcH 20.8 3.5 66.6 9.476040 3.8082e−11 1.00000 B 0.312312 0.052751 DHxK CCcH 14.5 1.4 46.3 11.115290 3.8920e−11 1.00000 B 0.313175 0.030826 ISxE CChH 56.6 24.8 386.1 6.605482 3.9718e−11 1.00000 N 0.146594 0.064198 RMxT HHcC 13.8 1.4 24.9 10.680289 4.2758e−11 1.00000 B 0.554217 0.057195 ANxP HHcC 30.6 10.3 110.0 6.640679 4.6760e−11 1.00000 N 0.278182 0.093685 LSxG HHcC 39.7 15.0 242.9 6.598851 5.0502e−11 1.00000 N 0.163442 0.061625 GLxR CHhH 21.8 5.9 145.6 6.672827 5.1373e−11 1.00000 N 0.149725 0.040593 YVVxD CCeE 6.6 0.1 6.5 18.333825 6.7702e−11 1.00000 B 1.015385 0.018971 DAxG HHhC 38.6 14.7 177.7 6.514124 8.9759e−11 1.00000 N 0.217220 0.082658 QGxG CChH 17.2 2.5 46.0 9.594800 9.0059e−11 1.00000 B 0.373913 0.054045 EGxT ECcE 26.5 8.5 78.0 6.552315 9.4222e−11 1.00000 N 0.339744 0.108760 SGxW CCcE 20.7 5.6 91.2 6.551699 1.1925e−10 1.00000 N 0.226974 0.061790 KExG HHhC 110.3 62.5 581.6 6.398256 1.2154e−10 1.00000 N 0.189649 0.107478 QExG HHhC 44.7 18.4 194.8 6.446972 1.2707e−10 1.00000 N 0.229466 0.094406 KSxW CChH 17.5 2.5 59.4 9.591293 1.6500e−10 1.00000 B 0.294613 0.042780 CGxC CCcH 9.9 0.5 42.7 13.508852 1.7531e−10 1.00000 B 0.231850 0.011494

TABLE 11 In Expected P-Value P-Value Observed Null Sequence Structure Epitopes in Epi In PDB Z-Score Upper Lower Distribution Ratio Probability GKTT CHHH 76.5 5.5 253.6 30.574180 9.6042e−203 1.00000 N 0.301656 0.021730 GKST CHHH 46.3 5.3 197.6 18.047241 2.1757e−71 1.00000 N 0.234312 0.026836 VGKS CCHH 47.9 1.7 155.8 35.415804 7.1871e−54 1.00000 B 0.307445 0.011035 AGKT CCHH 35.5 0.7 86.1 40.746053 2.0004e−49 1.00000 B 0.412311 0.008528 GVGK CCCH 47.2 2.5 185.6 28.170650 9.8957e−45 1.00000 B 0.254310 0.013725 GSGK CCCH 41.1 2.5 156.8 24.822233 1.5821e−37 1.00000 B 0.262117 0.015699 TGKT CCHH 39.3 2.7 129.9 22.607690 4.6581e−34 1.00000 B 0.302540 0.020625 VACK ECCC 33.2 2.4 45.0 20.373654 1.4230e−32 1.00000 B 0.737778 0.053619 CSAG CCCC 18.6 0.2 56.3 45.155914 2.7647e−32 1.00000 B 0.330373 0.002969 KVDK EEEE 99.7 35.9 374.1 11.193395 5.8880e−29 1.00000 N 0.266506 0.096012 TKVD EEEE 98.5 36.0 385.6 10.933259 1.0444e−27 1.00000 N 0.255446 0.093416 GAGK CCCH 28.8 1.8 99.9 20.625737 2.2129e−26 1.00000 B 0.288288 0.017523 CKNG CCCC 32.8 3.1 60.3 17.224893 5.4973e−26 1.00000 B 0.543947 0.051900 STKV CEEE 69.5 22.3 234.9 10.494679 1.4747e−25 1.00000 N 0.295871 0.095048 GSCW CCHH 12.8 0.1 33.8 46.433544 1.4522e−24 1.00000 B 0.378698 0.002227 NVAC EECC 26.5 1.9 49.4 18.344959 1.9069e−24 1.00000 B 0.536437 0.037918 GKTS CHHH 25.4 1.6 64.9 19.094604 8.3481e−24 1.00000 B 0.391371 0.024554 SGKT CCHH 28.0 2.2 126.7 17.503774 1.0663e−22 1.00000 B 0.220994 0.017439 GTGK CCCH 28.6 2.3 128.1 17.567876 1.1598e−22 1.00000 B 0.223263 0.017834 FTNS CHHH 25.7 2.1 47.2 16.829282 2.2403e−22 1.00000 B 0.544492 0.043704 GSCW ECHH 11.0 0.1 27.3 39.303420 1.3941e−21 1.00000 B 0.402930 0.002837 SGKS CCHH 21.9 1.2 111.0 19.363958 3.2639e−21 1.00000 B 0.197297 0.010445 VGKT CCHH 25.3 1.9 136.0 17.189134 7.3292e−21 1.00000 B 0.186029 0.013839 DKEG HHHC 26.2 5.5 57.6 9.268980 7.4842e−20 1.00000 N 0.454861 0.095656 FPGH CCCH 11.5 0.2 16.2 28.669589 1.9821e−19 1.00000 B 0.709877 0.009756 WCGP CCHH 23.2 2.1 48.1 14.990162 3.7261e−19 1.00000 B 0.482328 0.043149 GFTN CCHH 28.4 4.0 44.3 12.702991 6.0926e−19 1.00000 B 0.641084 0.091314 LTDW ECCC 10.1 0.1 11.0 26.776988 1.1021e−18 1.00000 B 0.918182 0.012740 PGPP CCCC 27.7 3.6 50.4 13.137686 1.2393e−18 1.00000 B 0.549603 0.071817 QFNT CECC 19.8 1.6 28.2 15.038708 1.4634e−18 1.00000 B 0.702128 0.055230 TQTG CCCC 23.0 2.4 39.9 13.827921 1.8451e−18 1.00000 B 0.576441 0.059320 LNHA CCEE 11.1 0.2 20.0 25.694482 5.0337e−18 1.00000 B 0.555000 0.009110 GKSS CHHH 19.2 1.2 65.2 16.561873 5.3468e−18 1.00000 B 0.294479 0.018451 QHFK EEEE 15.5 1.0 16.0 14.980105 6.5038e−18 1.00000 B 0.968750 0.062464 SSTK HCEE 54.6 18.9 198.1 8.640682 7.9973e−18 1.00000 N 0.275618 0.095330 RWNR CCCH 2.0 0.2 2.0 4.893270 3.1595e−17 1.00000 B 1.000000 0.077089 NVGK CCCH 13.5 0.4 31.0 20.335166 4.2581e−17 1.00000 B 0.435484 0.013530 ACKN CCCC 22.1 2.3 44.0 13.351970 4.5720e−17 1.00000 B 0.502273 0.052665 NAGK CCCH 9.8 0.1 18.7 30.350479 6.7477e−17 1.00000 B 0.524064 0.005489 HTFI ECCC 1.0 0.1 1.0 3.375835 1.0207e−16 1.00000 B 1.000000 0.080669 EAHV CCCE 1.0 0.1 1.0 3.921514 1.0424e−16 1.00000 B 1.000000 0.061056 FADK EEEC 1.5 0.1 1.0 3.999796 1.0449e−16 1.00000 B 1.500000 0.058829 FHIS HCCC 1.8 0.1 1.0 4.020228 1.0455e−16 1.00000 B 1.800000 0.058267 ADKL EECC 1.7 0.1 1.0 4.062022 1.0468e−16 1.00000 B 1.700000 0.057143 AGKS CCHH 14.6 0.6 40.6 18.684159 1.0527e−16 1.00000 B 0.359606 0.014083 TFGK ECCH 1.0 0.0 1.0 4.763663 1.0634e−16 1.00000 B 1.000000 0.042207 ANHI HHCC 1.0 0.0 1.0 4.967051 1.0670e−16 1.00000 B 1.000000 0.038954 YIKI EECC 1.5 0.0 1.0 5.722446 1.0773e−16 1.00000 B 1.500000 0.029633 AGMD CCEC 1.3 0.0 1.0 6.850790 1.0871e−16 1.00000 B 1.300000 0.020862 LFLE CHHH 1.0 0.0 1.0 7.222429 1.0893e−16 1.00000 B 1.000000 0.018810 VATS ECHH 1.5 0.0 1.0 19.687447 1.1074e−16 1.00000 B 1.500000 0.002573 GLGF ECCE 8.5 0.1 11.4 32.451180 2.0417e−16 1.00000 B 0.745614 0.005958 QEVI CCCC 17.0 1.4 24.7 13.695861 2.5094e−16 1.00000 B 0.688259 0.055787 MELC EECC 9.0 0.1 12.1 25.465608 2.7631e−16 1.00000 B 0.743802 0.010146 MDSS ECCC 14.9 0.7 43.2 17.357420 4.1795e−16 1.00000 B 0.344907 0.015781 QTGK CCCH 16.3 1.5 18.2 12.705645 4.9345e−16 1.00000 B 0.895604 0.081365 PSVY CEEE 17.5 1.1 268.7 15.823536 1.2792e−15 1.00000 B 0.065128 0.004023 TPNR CHHH 22.0 2.6 54.2 12.385370 1.5783e−15 1.00000 B 0.405904 0.047623 KPLY CCCC 17.3 1.9 20.1 11.920519 1.7658e−15 1.00000 B 0.860697 0.092045 GNLA CCCE 10.0 0.3 11.0 18.159308 1.9656e−15 1.00000 B 0.909091 0.026686 AAGK CCCH 13.3 0.6 36.1 16.855814 5.6027e−15 1.00000 B 0.368421 0.016035 YSTM CCCE 19.6 2.1 42.7 12.437257 1.1609e−14 1.00000 B 0.459016 0.048830 MNIF CCHH 20.6 2.5 41.1 11.694370 2.3532e−14 1.00000 B 0.501217 0.061842 TGNT CCHH 13.5 0.9 18.9 14.035756 2.9887e−14 1.00000 B 0.714286 0.045000 NICR CCCH 5.0 0.0 10.8 62.091204 3.1714e−14 1.00000 B 0.462963 0.000599 QDKE HHHH 23.7 5.9 64.0 7.716774 3.1832e−14 1.00000 N 0.370312 0.091796 FNTN ECCC 18.2 1.9 37.6 12.129079 3.7927e−14 1.00000 B 0.484043 0.050580 SGRT CCCC 23.0 5.5 88.8 7.691022 3.9756e−14 1.00000 N 0.259009 0.062075 YRDV CCCC 15.5 1.2 27.6 13.113855 5.0190e−14 1.00000 B 0.561594 0.044865 VNHG CCEE 7.8 0.1 9.0 26.302593 5.5620e−14 1.00000 B 0.866667 0.009648 VDKK EEEE 78.6 36.1 374.6 7.428060 1.0634e−13 1.00000 N 0.209824 0.096500 GKSA CHHH 15.8 1.2 56.8 13.676079 1.1247e−13 1.00000 B 0.278169 0.020574 GLTD EECC 10.6 0.5 11.4 14.766307 1.9385e−13 1.00000 B 0.929825 0.042968 FTVA CCHH 13.1 0.9 19.6 12.935319 2.1141e−13 1.00000 B 0.668367 0.047415 GGFM CCCH 10.0 0.5 10.7 13.957613 2.1432e−13 1.00000 B 0.934579 0.045486 PPGP CCCC 25.6 4.3 82.9 10.497601 2.2505e−13 1.00000 B 0.308806 0.052246 PTWN CEEC 13.5 0.5 10.5 13.872045 2.4774e−13 1.00000 B 1.285714 0.051741 STMS CCEE 14.9 1.1 42.8 13.377328 2.6426e−13 1.00000 B 0.348131 0.025541 GVCS CHHH 7.5 0.1 13.0 26.334228 2.7609e−13 1.00000 B 0.576923 0.006145 YASG HHCC 17.3 1.9 36.0 11.586737 3.4799e−13 1.00000 B 0.480556 0.051958 GGLM CCCH 12.2 0.7 19.9 13.592519 4.8030e−13 1.00000 B 0.613065 0.037107 DACQ ECCC 7.1 0.1 26.6 26.117565 7.6453e−13 1.00000 B 0.266917 0.002729 GLGR CHHH 11.0 0.6 16.8 13.543928 1.2177e−12 1.00000 B 0.654762 0.036346 VSWG EEEC 13.9 0.9 142.4 13.792449 1.5390e−12 1.00000 B 0.097612 0.006283 DSVT EEEE 20.6 3.2 45.4 10.115672 2.6490e−12 1.00000 B 0.453744 0.070196 GIMS CHHH 5.0 0.0 5.0 31.463022 3.2056e−12 1.00000 B 1.000000 0.005026 SGVG CCCC 20.6 5.0 135.3 7.083857 3.5288e−12 1.00000 N 0.152254 0.037119 WNIG ECCC 12.3 0.5 9.3 12.738906 6.1148e−12 1.00000 B 1.322581 0.054202 DSCQ ECCC 7.8 0.1 72.0 22.511242 8.3027e−12 1.00000 B 0.108333 0.001621 QTPN HCHH 22.1 4.1 46.3 9.249495 8.5114e−12 1.00000 B 0.477322 0.089425 KSRW CCHH 15.6 1.6 45.6 11.351320 8.7811e−12 1.00000 B 0.342105 0.034653 STVE EEEE 17.0 2.4 30.0 9.755365 1.1687e−11 1.00000 B 0.566667 0.080927 ACNG CCCC 7.0 0.2 9.0 17.192673 2.0549e−11 1.00000 B 0.777778 0.017901 GACW ECHH 5.7 0.0 4.0 40.933013 3.2174e−11 1.00000 B 1.425000 0.002382 GVGR CCHH 7.3 0.1 23.6 19.823519 3.2681e−11 1.00000 B 0.309322 0.005572 AGIG CCCH 5.9 0.0 26.5 30.927404 3.4380e−11 1.00000 B 0.222642 0.001358 HGKT CCHH 8.0 0.2 36.2 16.510870 5.6930e−11 1.00000 B 0.220994 0.006166 TLIS EEEE 13.7 1.3 44.6 11.229338 7.1321e−11 1.00000 B 0.307175 0.028307 NTKV CEEE 38.0 14.4 156.3 6.545601 7.4133e−11 1.00000 N 0.243122 0.091884

TABLE 12 In Expected P-Value P-Value Observed Null Sequence Structure Epitopes in Epi In PDB Z-Score Upper Lower Distribution Ratio Probability ExxxR HhhhH 3545.7 1634.5 12751.1 50.628214 0.0000e+00 1.00000 N 0.278070 0.128187 RxxxE HhhhH 2928.1 1427.8 11214.8 42.503045 0.0000e+00 1.00000 N 0.261092 0.127313 QxxxD HhhhH 1521.3 666.8 5548.2 35.277704 1.3372e−272 1.00000 N 0.274197 0.120187 RxxxR HhhhH 1627.7 735.0 5837.9 35.218117 1.0581e−271 1.00000 N 0.278816 0.125905 ExxxE HhhhH 2968.6 1676.2 12774.8 33.866288 1.6289e−251 1.00000 N 0.232379 0.131213 DxxxR HhhhH 1593.6 739.8 6057.4 33.503679 4.1121e−246 1.00000 N 0.263083 0.122130 ExxxQ HhhhH 1903.9 965.9 7773.1 32.250622 3.0026e−228 1.00000 N 0.244934 0.124264 AxxxR HhhhH 1716.6 888.8 9975.9 29.093571 3.6109e−186 1.00000 N 0.172075 0.089093 QxxxR HhhhH 1090.8 488.7 4100.8 29.020942 3.6056e−185 1.00000 N 0.265997 0.119170 AxxxA HhhhH 2239.1 1243.1 25522.9 28.964033 1.4239e−184 1.00000 N 0.087729 0.048705 QxxxQ HhhhH 1076.2 488.7 4171.0 28.285687 5.1236e−176 1.00000 N 0.258020 0.117162 QxxxE HhhhH 1661.6 884.6 7199.7 27.894386 2.5759e−171 1.00000 N 0.230787 0.122866 ExxxA HhhhH 2448.2 1446.9 14973.0 27.696798 5.5984e−169 1.00000 N 0.163508 0.096632 AxxxQ HhhhH 1200.9 575.4 6408.2 27.329373 1.7264e−164 1.00000 N 0.187401 0.089798 RxxxQ HhhhH 1065.6 500.0 4150.3 26.972525 2.9554e−160 1.00000 N 0.256753 0.120469 ExxxK HhhhH 3252.3 2124.9 15568.8 26.317913 8.1352e−153 1.00000 N 0.208899 0.136488 ExxxL HhhhH 1724.7 952.4 13302.4 25.973127 7.7159e−149 1.00000 N 0.129653 0.071595 QxxxN HhhhH 782.6 336.4 3046.6 25.795862 1.0406e−146 1.00000 N 0.256877 0.110409 KxxxE HhhhH 2766.8 1765.1 13152.5 25.624911 5.5898e−145 1.00000 N 0.210363 0.134200 RxxxL HhhhH 1346.1 698.5 9345.2 25.474971 3.0835e−143 1.00000 N 0.144042 0.074742 LxxxR HhhhH 1256.2 640.3 9084.4 25.244635 1.0887e−140 1.00000 N 0.138281 0.070486 LxxxE HhhhH 1373.3 739.2 9254.6 24.314227 1.1055e−130 1.00000 N 0.148391 0.079873 NxxxR HhhhH 648.3 270.4 2518.1 24.322629 1.2367e−130 1.00000 N 0.257456 0.107389 RxxxD HhhhH 1124.8 579.6 4662.5 24.197519 2.0224e−129 1.00000 N 0.241244 0.124320 ExxxN HhhhH 1238.3 662.5 5424.4 23.874648 4.6110e−126 1.00000 N 0.228283 0.122138 ExxxS HhhhH 1260.4 676.4 5947.2 23.853305 7.6202e−126 1.00000 N 0.211932 0.113731 YxxxN HhhhH 359.7 114.6 1469.5 23.835304 2.2944e−125 1.00000 N 0.244777 0.078017 AxxxE HhhhH 1813.4 1077.4 10751.7 23.638803 1.1253e−123 1.00000 N 0.168662 0.100207 QxxxA HhhhH 1147.9 606.8 7180.5 22.960147 9.5018e−117 1.00000 N 0.159864 0.084501 QxxxL HhhhH 851.0 410.1 7080.9 22.428266 1.8468e−111 1.00000 N 0.120182 0.057922 NxxxQ HhhhH 622.8 276.1 2608.8 22.070213 6.1727e−108 1.00000 N 0.238730 0.105815 KxxxD HhhhH 1559.9 937.5 7193.2 21.796348 1.8415e−105 1.00000 N 0.216858 0.130335 LxxxQ HhhhH 838.5 412.3 6031.4 21.746653 6.4761e−105 1.00000 N 0.139022 0.068358 YxxxR HhhhH 507.5 207.9 2808.6 21.590025 2.4287e−103 1.00000 N 0.180695 0.074032 PxxxR HhhhH 719.8 345.7 3048.4 21.371192 2.2826e−101 1.00000 N 0.236124 0.113393 RxxxA HhhhH 1371.7 800.6 8918.1 21.157309 1.7498e−99 1.00000 N 0.153811 0.089769 YxxxK HhhhH 681.0 320.1 3778.3 21.088212 9.4565e−99 1.00000 N 0.180240 0.084710 TxxxQ HhhhH 624.6 288.5 2880.6 20.861512 1.1458e−96 1.00000 N 0.216830 0.100147 DxxxE HhhhH 1501.2 918.8 7072.8 20.599825 1.9838e−94 1.00000 N 0.212250 0.129901 SxxxR HhhhH 800.7 407.6 4098.8 20.521420 1.1851e−93 1.00000 N 0.195350 0.099432 YxxxL HhhhH 540.6 236.8 6880.9 20.088526 9.0430e−90 1.00000 N 0.078565 0.034417 RxxxN HhhhH 653.6 316.9 2892.5 20.040727 2.2101e−89 1.00000 N 0.225964 0.109571 KxxxR HhhhH 1011.6 569.9 4523.9 19.791965 2.7224e−87 1.00000 N 0.223612 0.125972 DxxxQ HhhhH 930.8 512.8 4144.6 19.719888 1.1598e−86 1.00000 N 0.224581 0.123724 SxxxQ HhhhH 680.2 338.0 3360.0 19.626339 8.0947e−86 1.00000 N 0.202440 0.100596 VxxxE HhhhH 776.9 402.6 5432.9 19.383764 8.7489e−84 1.00000 N 0.142999 0.074111 SxxxE HhhhH 986.8 556.7 5025.9 19.331093 2.2728e−83 1.00000 N 0.196343 0.110765 HxxxE HhhhH 519.1 238.2 2247.4 19.253484 1.2780e−82 1.00000 N 0.230978 0.105970 AxxxD HhhhH 831.5 447.2 4633.8 19.121192 1.3547e−81 1.00000 N 0.179442 0.096500 AxxxS HhhhH 815.9 432.0 6889.2 19.076253 3.1981e−81 1.00000 N 0.118432 0.062711 DxxxA HhhhH 1305.7 800.2 8841.7 18.737176 1.7447e−78 1.00000 N 0.147675 0.090505 LxxxE CchhH 488.7 220.5 3253.3 18.701598 4.6170e−78 1.00000 N 0.150217 0.067791 ExxxD HhhhH 1027.9 600.3 4905.2 18.630742 1.3593e−77 1.00000 N 0.209553 0.122376 SxxxA HhhhH 836.8 452.6 7696.8 18.615784 1.8805e−77 1.00000 N 0.108721 0.058802 TxxxR HhhhH 665.8 341.1 3439.7 18.522474 1.1550e−76 1.00000 N 0.193563 0.099169 IxxxE HhhhH 652.2 328.6 4866.2 18.486861 2.2361e−76 1.00000 N 0.134027 0.067526 SxxxH HhhhH 315.2 120.9 1433.7 18.466932 4.5899e−76 1.00000 N 0.219851 0.084326 QxxxS HhhhH 623.3 314.0 3007.9 18.442239 5.2220e−76 1.00000 N 0.207221 0.104399 LxxxQ CchhH 328.0 127.5 1903.8 18.382341 2.1159e−75 1.00000 N 0.172287 0.066973 PxxxA HhhhH 816.8 444.6 6116.7 18.331464 3.6493e−75 1.00000 N 0.133536 0.072684 FxxxQ HhhhH 322.3 125.4 2057.5 18.151574 1.4421e−73 1.00000 N 0.156646 0.060927 ExxxY HhhhH 629.3 321.2 3734.6 17.978943 2.4098e−72 1.00000 N 0.168505 0.086016 YxxxQ HhhhH 376.9 159.4 2150.4 17.908928 1.0512e−71 1.00000 N 0.175270 0.074107 KxxxQ HhhhH 1012.7 602.6 4794.5 17.866819 1.5795e−71 1.00000 N 0.211221 0.125685 VxxxR HhhhH 729.3 391.2 5584.0 17.726047 2.1028e−70 1.00000 N 0.130605 0.070058 IxxxN HhhhH 403.8 176.6 2697.7 17.686932 5.2702e−70 1.00000 N 0.149683 0.065459 NxxxE HhhhH 854.2 488.3 4085.1 17.649644 7.8447e−70 1.00000 N 0.209101 0.119520 ExxxI HhhhH 758.2 412.4 6102.5 17.633481 1.0697e−69 1.00000 N 0.124244 0.067581 IxxxR HhhhH 603.5 306.0 4707.3 17.585071 2.6989e−69 1.00000 N 0.128205 0.065013 CxxxH HhhhH 107.1 23.6 476.2 17.656516 2.9300e−69 1.00000 N 0.224906 0.049463 MxxxE CchhH 292.0 113.4 1275.4 17.563916 5.5301e−69 1.00000 N 0.228948 0.088946 NxxxS HhhhH 514.3 251.1 2512.2 17.506813 1.1392e−68 1.00000 N 0.204721 0.099956 QxxxT HhhhH 555.2 279.9 2775.6 17.354733 1.5715e−67 1.00000 N 0.200029 0.100838 HxxxQ HhhhH 327.4 136.5 1404.3 17.198608 2.9556e−66 1.00000 N 0.233141 0.097192 VxxxN HhhhH 437.6 204.7 2937.8 16.882201 5.6161e−64 1.00000 N 0.148955 0.069662 DxxxS HhhhH 723.1 404.9 3662.5 16.770933 3.1011e−63 1.00000 N 0.197433 0.110539 DxxxD HhhhH 761.9 435.3 3587.0 16.698203 1.0362e−62 1.00000 N 0.212406 0.121362 SxxxS HhhhH 612.2 324.9 3868.8 16.653077 2.3318e−62 1.00000 N 0.158240 0.083981 PxxxE HhhhH 874.8 522.0 4147.7 16.516679 2.0506e−61 1.00000 N 0.210912 0.125850 FxxxR HhhhH 380.5 171.4 2686.2 16.507278 3.1248e−61 1.00000 N 0.141650 0.063807 TxxxE HhhhH 774.7 446.4 4237.2 16.426992 9.2564e−61 1.00000 N 0.182833 0.105356 WxxxQ HhhhH 201.9 69.9 1001.1 16.362918 4.8607e−60 1.00000 N 0.201678 0.069854 LxxxH HhhhH 363.9 162.7 3238.0 16.184271 6.2530e−59 1.00000 N 0.112384 0.050250 IxxxQ HhhhH 400.2 186.3 3042.8 16.174438 7.0518e−59 1.00000 N 0.131524 0.061226 DxxxK HhhhH 1418.7 960.1 7235.1 15.890960 4.8245e−57 1.00000 N 0.196086 0.132705 ExxxT HhhhH 863.4 520.4 5003.9 15.884514 5.8664e−57 1.00000 N 0.172545 0.103999 RxxxK HhhhH 1047.0 667.3 5094.2 15.769294 3.5148e−56 1.00000 N 0.205528 0.130986 NxxxN HhhhH 411.8 201.8 1933.5 15.625829 4.3487e−55 1.00000 N 0.212982 0.104345 HxxxR HhhhH 321.8 143.5 1583.7 15.607413 6.4283e−55 1.00000 N 0.203195 0.090614 NxxxL HhhhH 450.7 223.9 4154.2 15.578085 8.7727e−55 1.00000 N 0.108493 0.053909 SxxxN HhhhH 487.3 253.1 2480.3 15.534756 1.6921e−54 1.00000 N 0.196468 0.102045 DxxxN HhhhH 594.3 330.2 2767.7 15.489774 3.2073e−54 1.00000 N 0.214727 0.119292 ExxxH HhhhH 551.1 300.0 2737.5 15.360468 2.4145e−53 1.00000 N 0.201315 0.109602 YxxxE HhhhH 396.8 192.7 2422.9 15.323125 4.7702e−53 1.00000 N 0.163771 0.079539 LxxxN HhhhH 499.1 260.5 3907.2 15.305012 5.7912e−53 1.00000 N 0.127739 0.066663 PxxxQ HhhhH 489.4 259.6 2215.5 15.182747 3.8046e−52 1.00000 N 0.220898 0.117159 QxxxW HhhhH 165.8 55.6 973.5 15.206793 4.5631e−52 1.00000 N 0.170313 0.057164 ExxxR HhhhC 358.1 171.9 1395.4 15.161362 5.9193e−52 1.00000 N 0.256629 0.123222 LxxxL HhhhH 997.1 625.8 27017.2 15.017249 3.8391e−51 1.00000 N 0.036906 0.023163

TABLE 13 In Expected P-Value P-Value Observed Null Sequence Structure Epitopes in Epi In PDB Z-Score Upper Lower Distribution Ratio Probability NxxDL EccCC 52.0 5.7 142.7 19.794530 1.1279e−85 1.00000 N 0.364401 0.039936 TxxGK CccCH 57.5 7.2 179.0 19.161164 1.4880e−80 1.00000 N 0.321229 0.040133 SxxYH HhhHH 55.1 7.3 104.0 18.276180 2.0986e−73 1.00000 N 0.529808 0.070636 GxxKS CccHH 81.1 15.9 322.6 16.741561 2.8010e−62 1.00000 N 0.251395 0.049402 CxxCH HhhCC 51.8 7.9 109.2 16.170548 7.9700e−58 1.00000 N 0.474359 0.072665 ExxRR HhhHH 299.8 133.8 1539.6 15.024308 5.0311e−51 1.00000 N 0.194726 0.086878 CxxCH HhhHH 52.6 9.3 112.0 14.780082 1.2263e−48 1.00000 N 0.469643 0.083434 SxxGK CccCH 44.6 6.8 222.2 14.731787 3.5333e−48 1.00000 N 0.200720 0.030575 GxxKT CccHH 72.0 15.7 369.5 14.495654 4.1781e−47 1.00000 N 0.194858 0.042587 AxxAA HhhHH 232.6 96.4 3380.2 14.070952 5.9399e−45 1.00000 N 0.068812 0.028524 CxxCH ChhHH 41.5 2.9 62.5 23.302795 9.4544e−40 1.00000 B 0.664000 0.046071 ExxRL HhhHH 194.4 85.3 1592.4 12.143932 6.0904e−34 1.00000 N 0.122080 0.053562 YxxEN HhhHH 47.1 12.1 158.4 10.435507 4.0653e−25 1.00000 N 0.297348 0.076699 ExxRE HhhHH 240.2 130.3 1378.1 10.115517 3.7685e−24 1.00000 N 0.174298 0.094564 AxxTT CchHH 31.4 3.0 95.3 16.791123 1.7851e−23 1.00000 B 0.329486 0.031067 DxxRR HhhHH 121.9 52.8 600.5 9.963409 2.2695e−23 1.00000 N 0.202998 0.087883 AxxRR HhhHH 119.0 51.0 722.4 9.873794 5.5640e−23 1.00000 N 0.164729 0.070617 DxxGK CccCH 31.4 3.2 84.3 16.156690 6.4849e−23 1.00000 B 0.372479 0.037626 ExxRA HhhHH 216.7 115.4 1491.6 9.812480 8.0321e−23 1.00000 N 0.145280 0.077390 PxxGK CccCH 37.1 8.6 207.4 9.893210 1.2460e−22 1.00000 N 0.178881 0.041644 YxxGR HhcCC 27.9 5.6 83.6 9.814050 4.2178e−22 1.00000 N 0.333732 0.066430 AxxER HhhHH 160.2 78.8 960.0 9.579453 8.6052e−22 1.00000 N 0.166875 0.082033 CxxCW CecHH 10.1 0.0 32.8 49.128009 8.8894e−22 1.00000 B 0.307927 0.001280 QxxAA HhhHH 119.9 52.6 1024.0 9.528485 1.5740e−21 1.00000 N 0.117090 0.051362 HxxNE HhhHH 36.8 9.1 122.0 9.582928 2.4752e−21 1.00000 N 0.301639 0.074219 RxxMD HhhEC 17.1 0.6 44.2 22.238496 2.7644e−21 1.00000 B 0.386878 0.012675 NxxCK EecCC 24.2 2.0 45.0 15.927613 6.0120e−21 1.00000 B 0.537778 0.045091 AxxRA HhhHH 165.8 82.7 1804.6 9.359131 6.8374e−21 1.00000 N 0.091876 0.045813 ExxRQ HhhHH 149.6 73.1 886.5 9.344841 8.1784e−21 1.00000 N 0.168754 0.082435 ExxAA HhhHC 52.1 16.1 214.0 9.306055 2.2237e−20 1.00000 N 0.243458 0.075445 PxxNI CeeCC 14.4 0.5 13.3 19.167577 1.9524e−19 1.00000 B 1.082707 0.034936 QxxEG HhhHC 34.9 8.9 104.9 9.070130 2.9112e−19 1.00000 N 0.332698 0.085314 SxxAA HhhHH 78.9 30.6 960.7 8.862496 8.8792e−19 1.00000 N 0.082128 0.031889 AxxAR HhhHH 118.4 54.8 1244.1 8.783439 1.4619e−18 1.00000 N 0.095169 0.044062 AxxSQ HhhHC 32.8 8.4 98.7 8.827817 2.6401e−18 1.00000 N 0.332320 0.084790 AxxEA HhhHH 188.2 103.4 2180.2 8.538938 1.0460e−17 1.00000 N 0.086322 0.047445 GxxNS CchHH 25.9 3.1 66.8 13.347601 1.3878e−17 1.00000 B 0.387725 0.045915 NxxPN HhcHH 25.0 5.6 53.4 8.621938 2.2460e−17 1.00000 N 0.468165 0.105585 SxxGN CccCH 16.7 1.1 22.8 15.333850 3.2588e−17 1.00000 B 0.732456 0.047742 YxxNF CccCC 23.9 5.1 96.2 8.563062 3.8617e−17 1.00000 N 0.248441 0.052944 SxxVD CeeEE 71.1 28.4 311.2 8.413504 4.5859e−17 1.00000 N 0.228470 0.091179 ExxLA HhhHH 172.9 94.5 1763.6 8.285516 9.1556e−17 1.00000 N 0.098038 0.053601 HxxQA HhhCH 1.0 0.1 1.0 3.306715 1.0172e−16 1.00000 B 1.000000 0.083792 ExxAA HhhHH 179.9 99.7 1794.4 8.266710 1.0592e−16 1.00000 N 0.100256 0.055555 TxxDK EeeEE 91.2 40.9 412.9 8.290419 1.1242e−16 1.00000 N 0.220877 0.099016 RxxRE HhhHH 141.4 74.0 828.4 8.217981 1.7164e−16 1.00000 N 0.170690 0.089275 VxxHE HhhHH 28.9 4.0 173.8 12.540326 2.2042e−16 1.00000 B 0.166283 0.023172 KxxGA HhcCC 44.0 13.9 283.3 8.262977 2.2260e−16 1.00000 N 0.155312 0.049167 RxxGI HhcCC 41.0 12.7 265.2 8.142027 6.3123e−16 1.00000 N 0.154600 0.047865 AxxRT HccCC 23.5 5.3 79.3 8.142951 1.1990e−15 1.00000 N 0.296343 0.067278 VxxGA HhcCC 33.4 9.3 235.9 8.076537 1.2963e−15 1.00000 N 0.141585 0.039348 KxxGF HhcCC 37.3 11.3 204.8 7.969461 2.7196e−15 1.00000 N 0.182129 0.055082 AxxRD HhhHH 77.3 33.4 420.4 7.903500 2.7836e−15 1.00000 N 0.183873 0.079560 CxxCH CccCC 24.7 5.9 98.0 8.021387 2.8947e−15 1.00000 N 0.252041 0.059844 AxxAS HhhHH 77.3 33.1 862.3 7.834917 4.7308e−15 1.00000 N 0.089644 0.038384 AxxAE HhhHH 133.4 70.4 1311.8 7.716222 9.6679e−15 1.00000 N 0.101692 0.053677 SxxGL HhhCC 27.2 7.0 120.2 7.839361 1.0445e−14 1.00000 N 0.226290 0.058491 ExxGL HhcCC 64.7 26.4 437.9 7.674219 1.8107e−14 1.00000 N 0.147751 0.060392 VxxKN EccCC 29.4 8.2 105.5 7.747512 1.9363e−14 1.00000 N 0.278673 0.077267 LxxLH HhhHH 39.2 12.4 609.3 7.696374 2.1292e−14 1.00000 N 0.064336 0.020332 AxxRE HhhHH 138.9 75.7 940.9 7.575524 2.8327e−14 1.00000 N 0.147625 0.080452 ExxLS HhhHH 102.2 50.1 839.3 7.584261 2.9242e−14 1.00000 N 0.121768 0.059728 ExxGA HhhCC 41.1 13.7 243.7 7.613209 3.8832e−14 1.00000 N 0.168650 0.056268 KxxAC EeeCC 18.1 1.8 44.0 12.344442 3.9683e−14 1.00000 B 0.411364 0.041254 HxxKV HhhHH 33.0 9.8 164.9 7.631524 4.1038e−14 1.00000 N 0.200121 0.059517 AxxAA HhhHC 61.6 25.0 435.1 7.547460 4.8688e−14 1.00000 N 0.141577 0.057408 AxxGL HhhCC 41.1 13.8 280.1 7.540236 6.6990e−14 1.00000 N 0.146733 0.049246 SxxTT CchHH 22.4 3.0 85.8 11.509229 7.9920e−14 1.00000 B 0.261072 0.034452 AxxRH HhhHH 52.1 19.9 294.8 7.480402 8.9042e−14 1.00000 N 0.176730 0.067458 RxxGL HhcCC 53.5 20.6 336.0 7.465023 9.8050e−14 1.00000 N 0.159226 0.061435 CxxCH HhhHE 13.2 1.3 13.5 11.110583 1.4758e−13 1.00000 B 0.977778 0.094252 AxxAQ HhhHH 79.5 36.2 761.4 7.381135 1.4828e−13 1.00000 N 0.104413 0.047510 LxxNV CchHH 25.9 4.5 77.5 10.453245 1.5252e−13 1.00000 B 0.334194 0.057583 AxxQD HhhHH 65.9 28.4 324.1 7.377042 1.6844e−13 1.00000 N 0.203332 0.087528 GxxGK CccCH 26.0 6.8 249.5 7.472893 1.6894e−13 1.00000 N 0.104208 0.027222 MxxCT EecCC 8.0 0.1 11.6 20.815710 1.7845e−13 1.00000 B 0.689655 0.012433 PxxAA HhhHH 66.0 27.9 816.2 7.342254 2.1476e−13 1.00000 N 0.080863 0.034173 NxxHQ HhhHH 21.3 5.1 62.2 7.471413 2.2332e−13 1.00000 N 0.342444 0.082215 MxxSR HhhHC 19.9 2.5 52.1 11.260987 2.7264e−13 1.00000 B 0.381958 0.048106 KxxDG EccCC 71.2 31.9 339.7 7.297480 2.9121e−13 1.00000 N 0.209597 0.094033 DxxRA HhhHH 112.5 58.9 823.5 7.256832 3.2587e−13 1.00000 N 0.136612 0.071469 DxxRN HhhHC 24.5 6.5 74.9 7.380530 3.6042e−13 1.00000 N 0.327103 0.086891 AxxQA HhhHH 113.8 59.5 1177.6 7.223678 4.1184e−13 1.00000 N 0.096637 0.050530 DxxSN HhhHH 31.0 9.4 133.5 7.288476 5.4139e−13 1.00000 N 0.232210 0.070612 NxxRN HhhHH 33.2 10.6 140.1 7.236560 7.3844e−13 1.00000 N 0.236974 0.075474 ExxLP HhhCC 31.6 9.7 176.5 7.229156 8.0852e−13 1.00000 N 0.179037 0.054991 CxxNI EccCC 8.0 0.2 15.3 20.051595 8.1343e−13 1.00000 B 0.522876 0.010108 VxxTS CchHH 18.0 2.1 58.7 11.324529 9.1748e−13 1.00000 B 0.306644 0.035000 CxxCH HhhHC 21.4 3.5 40.7 10.054804 9.3614e−13 1.00000 B 0.525799 0.085377 CxxCW CccHH 6.6 0.0 35.7 33.489514 1.1250e−12 1.00000 B 0.184874 0.001076 QxxMS CchHH 7.0 0.1 8.0 20.029061 1.3328e−12 1.00000 B 0.875000 0.014974 PxxLT HhhHH 34.7 11.3 229.3 7.111345 1.7124e−12 1.00000 N 0.151330 0.049482 AxxQQ HhhHH 73.7 34.2 442.5 7.033591 1.8980e−12 1.00000 N 0.166554 0.077271 GxxAA HhhHH 53.5 21.4 1130.0 7.016140 2.4760e−12 1.00000 N 0.047345 0.018914 AxxGR CccHH 15.6 1.4 64.8 12.259572 2.5530e−12 1.00000 B 0.240741 0.021226 AxxDA HhhHH 99.9 51.3 1121.1 6.945769 3.1146e−12 1.00000 N 0.089109 0.045761 QxxGL CccCH 17.9 2.2 47.3 10.729026 4.0680e−12 1.00000 B 0.378436 0.047294 SxxDS HhhHH 28.9 8.9 121.4 6.997453 4.4603e−12 1.00000 N 0.238056 0.072925 QxxND HhhHH 36.3 12.7 151.8 6.922566 6.1794e−12 1.00000 N 0.239130 0.083607

TABLE 14 In Expected P-Value P-Value Observed Null Sequence Structure Epitopes in Epi In PDB Z-Score Upper Lower Distribution Ratio Probability GxGxS CcChH 90.7 18.3 441.1 17.277824 2.7158e−66 1.00000 N 0.205622 0.041517 GxGxT CcChH 82.9 19.3 472.3 14.775292 5.8901e−49 1.00000 N 0.175524 0.040888 AxKxT CcHhH 46.2 2.3 132.8 28.973360 3.8354e−46 1.00000 B 0.347892 0.017570 SxKxT CcHhH 45.9 2.3 169.0 28.763578 1.0498e−44 1.00000 B 0.271598 0.013768 VxKxS CcHhH 34.5 1.5 112.2 27.236570 1.7784e−36 1.00000 B 0.307487 0.013269 GxGxG CcChH 43.7 8.6 269.1 12.148832 2.3822e−33 1.00000 N 0.162393 0.032017 TxVxK EeEeE 106.2 37.4 568.5 11.640466 3.4471e−31 1.00000 N 0.186807 0.065781 SxKxD CeEeE 66.9 19.0 237.4 11.470166 3.6870e−30 1.00000 N 0.281803 0.079926 TxTxK CcCcH 29.5 1.8 56.2 20.951875 9.2706e−29 1.00000 B 0.524911 0.032121 VxCxN EcCcC 28.9 2.1 67.3 19.011379 1.1251e−25 1.00000 B 0.429421 0.030557 SxVxK CcCcH 25.8 1.9 101.1 17.528911 1.3538e−21 1.00000 B 0.255193 0.018747 GxTxS CcHhH 25.7 2.3 77.1 15.700551 6.1084e−20 1.00000 B 0.333333 0.029715 QxGxT CcChH 22.7 1.9 40.4 15.608649 9.3613e−20 1.00000 B 0.561881 0.046230 DxAxK CcCcH 22.0 1.7 62.2 15.851300 4.4906e−19 1.00000 B 0.353698 0.027136 KxDxK EeEeE 78.2 31.5 395.3 8.663783 5.1313e−18 1.00000 N 0.197824 0.079765 SxTxV HcEeE 67.5 26.5 339.7 8.277657 1.4600e−16 1.00000 N 0.198705 0.078155 SxTxN CcCcH 15.3 1.0 22.5 15.029372 3.7791e−16 1.00000 B 0.680000 0.042297 QxPxS EeCcE 34.5 9.6 273.2 8.163922 6.2295e−16 1.00000 N 0.126281 0.035226 QxKxG HhHhC 36.0 10.4 188.4 8.142734 7.1133e−16 1.00000 N 0.191083 0.055388 KxVxC EeEcC 19.9 1.9 57.7 13.267711 2.7457e−15 1.00000 B 0.344887 0.032977 NxAxK EeCcC 24.7 3.6 55.5 11.503434 4.7976e−15 1.00000 B 0.445045 0.064834 GxTxY CcEeE 52.6 19.4 391.0 7.732901 1.3037e−14 1.00000 N 0.134527 0.049610 RxKxG EcCcC 27.1 7.1 109.2 7.781732 1.6320e−14 1.00000 N 0.248168 0.064822 AxGxR HcCcC 36.6 11.5 170.4 7.680274 2.5874e−14 1.00000 N 0.214789 0.067340 SxGxG EeCcC 26.3 6.7 281.3 7.709803 2.8760e−14 1.00000 N 0.093494 0.023647 NxGxT CcChH 20.3 2.4 51.0 11.698574 5.4820e−14 1.00000 B 0.398039 0.047969 PxWxI CeEcC 12.3 0.3 9.3 15.817318 1.4860e−13 1.00000 B 1.322581 0.035840 SxGxG CcCcH 25.0 3.9 151.4 10.870832 1.7440e−13 1.00000 B 0.165125 0.025597 TxMxF CcCcC 18.4 2.0 52.3 11.772241 2.9763e−13 1.00000 B 0.351816 0.038525 GxSxE CcChH 87.9 42.3 619.0 7.264315 3.3686e−13 1.00000 N 0.142003 0.068333 RxRxG EcCcC 21.8 5.3 79.6 7.390263 3.8620e−13 1.00000 N 0.273869 0.066905 CxAxI CcCcC 15.6 1.3 50.1 12.992225 4.0316e−13 1.00000 B 0.311377 0.024970 RxSxT EeCcC 21.8 3.0 83.5 10.987197 5.0613e−13 1.00000 B 0.261078 0.036272 QxNxQ EeCcC 19.3 2.7 36.1 10.437162 9.0830e−13 1.00000 B 0.534626 0.075549 AxGxT HcCcC 38.3 13.1 237.7 7.177890 9.9181e−13 1.00000 N 0.161127 0.054993 CxGxH ChHhH 9.4 0.3 13.6 16.130102 1.8371e−12 1.00000 B 0.691176 0.023847 QxGxC CcCcH 12.3 0.8 22.2 12.974678 2.2038e−12 1.00000 B 0.554054 0.036647 QxNxN CeCcC 17.6 2.4 31.2 10.223071 5.2458e−12 1.00000 B 0.564103 0.076790 NxKxD CeEeE 36.1 12.5 155.1 6.939188 5.5327e−12 1.00000 N 0.232753 0.080856 QxPxR HcHhH 18.2 2.4 55.2 10.489330 7.0720e−12 1.00000 B 0.329710 0.043075 YxSxR HhCcC 18.3 2.5 49.8 10.332758 8.5782e−12 1.00000 B 0.367470 0.049592 MxIxE CcHhH 20.5 5.1 117.7 6.943104 9.2565e−12 1.00000 N 0.174172 0.043553 GxTxW EeCcC 9.1 0.4 14.3 14.427172 1.2572e−11 1.00000 B 0.636364 0.026262 GxExF CcCeE 20.1 5.0 116.8 6.848623 1.7824e−11 1.00000 N 0.172089 0.043222 DxNxE CcChH 25.1 7.3 128.5 6.781685 2.1820e−11 1.00000 N 0.195331 0.056827 VxKxC CcHhH 10.0 0.4 62.5 14.474398 2.4703e−11 1.00000 B 0.160000 0.007030 HxNxR EeEeE 10.4 0.5 41.7 14.375158 2.5174e−11 1.00000 B 0.249400 0.011550 CxNxQ CcCcC 20.1 3.1 82.3 9.762451 2.6118e−11 1.00000 B 0.244228 0.038133 AxVxR CcChH 10.8 0.6 30.0 13.215029 5.4998e−11 1.00000 B 0.360000 0.020240 KxGxT CcCcC 72.0 34.9 523.7 6.508995 6.7535e−11 1.00000 N 0.137483 0.066578 DxDxT CcCcE 20.6 5.5 97.6 6.635209 7.0133e−11 1.00000 N 0.211066 0.056280 ExGxS EcCcC 22.8 4.3 107.0 9.131379 8.1828e−11 1.00000 B 0.213084 0.040032 PxHxA CcHhH 13.8 1.3 42.8 11.025072 8.4644e−11 1.00000 B 0.322430 0.030883 GxLxL CcCcH 18.9 2.8 110.4 9.756476 8.9145e−11 1.00000 B 0.171196 0.025321 CxGxI EcCcC 7.0 0.2 19.8 17.719130 9.6238e−11 1.00000 B 0.353535 0.007605 QxQxN CcCeC 16.7 2.5 32.4 9.345434 1.2978e−10 1.00000 B 0.515432 0.077204 NxGxM EcCcH 8.1 0.3 12.3 13.702397 1.4709e−10 1.00000 B 0.658537 0.026861 MxLxT EeCcC 13.0 1.2 48.2 10.653411 2.0738e−10 1.00000 B 0.269710 0.025913 DxNxY CcCcE 20.3 5.6 84.7 6.441134 2.4504e−10 1.00000 N 0.239669 0.065956 TxKxT CcHhH 14.0 1.5 79.3 10.247023 3.4869e−10 1.00000 B 0.176545 0.019088 YxHxC CcCcC 7.0 0.3 8.0 13.107702 4.1509e−10 1.00000 B 0.875000 0.034088 DxPxY CcCcC 26.5 8.6 158.0 6.299163 4.5765e−10 1.00000 N 0.167722 0.054230 DxGxG CcCcC 70.9 35.3 709.9 6.151718 6.5827e−10 1.00000 N 0.099873 0.049697 NxTxN HhChH 18.4 3.3 47.3 8.623012 6.9892e−10 1.00000 B 0.389006 0.069712 PxSxK CcCcH 11.8 1.0 49.0 10.999112 7.9644e−10 1.00000 B 0.240816 0.020131 AxIxR CcCcH 10.8 0.8 37.9 11.351590 1.0590e−09 1.00000 B 0.284960 0.020941 CxGxS CcCcC 25.9 8.3 343.1 6.157692 1.0995e−09 1.00000 N 0.075488 0.024300 TxPxG EcCcC 38.8 15.5 285.9 6.068337 1.4435e−09 1.00000 N 0.135712 0.054349 GxLxH CcCeE 13.8 1.7 43.6 9.388972 2.2415e−09 1.00000 B 0.316514 0.039512 NxGxH EcCcE 11.7 1.1 56.8 10.371446 2.9851e−09 1.00000 B 0.205986 0.018848 GxVxK CcCcH 18.9 3.5 160.1 8.403678 3.7537e−09 1.00000 B 0.118051 0.021569 DxLxA HhCcH 14.8 2.1 66.2 9.025764 3.9660e−09 1.00000 B 0.223565 0.031075 VxKxA CcHhH 16.4 2.5 126.8 8.768982 4.4341e−09 1.00000 B 0.129338 0.020086 TxAxK CcCcH 11.1 1.1 35.8 9.811276 4.5969e−09 1.00000 B 0.310056 0.030060 VxPxY EcCcC 20.4 4.2 105.4 8.032775 4.7842e−09 1.00000 B 0.193548 0.040079 NxGxM HcCcH 6.6 0.2 7.8 13.426233 5.8155e−09 1.00000 B 0.846154 0.029725 KxNxY EeCcC 10.3 1.1 16.6 9.184465 8.7789e−09 1.00000 B 0.620482 0.064951 NxFxV HcCcH 6.3 0.2 8.0 12.666549 1.2366e−08 1.00000 B 0.787500 0.029519 GxSxL EeEcC 7.0 0.3 22.8 12.325790 1.2828e−08 1.00000 B 0.307018 0.013134 CxSxW CeChH 4.9 0.0 37.1 23.296904 1.3101e−08 1.00000 B 0.132075 0.001173 LxPxE CcChH 21.8 7.1 105.6 5.746143 1.4179e−08 1.00000 N 0.206439 0.066814 CxQxT CcEeE 11.5 1.3 36.0 9.258328 1.4559e−08 1.00000 B 0.319444 0.035176 SxSxN CcChH 18.1 5.3 85.1 5.748142 1.6594e−08 1.00000 N 0.212691 0.062200 QxRxY CcCcH 7.8 0.5 10.1 10.639154 1.7285e−08 1.00000 B 0.772277 0.049077 CxAxH ChHhH 9.0 0.7 37.3 10.163442 1.9366e−08 1.00000 B 0.241287 0.018291 NxGxS CcChH 14.8 2.4 58.5 8.220381 2.1270e−08 1.00000 B 0.252991 0.040678 LxFxI CcEeE 10.2 0.9 64.5 9.774234 2.1939e−08 1.00000 B 0.158140 0.014191 NxQxQ CcCcC 26.5 9.7 142.4 5.615982 2.5284e−08 1.00000 N 0.186096 0.067789 LxVxY CcCeE 9.4 0.8 32.2 9.906317 3.0929e−08 1.00000 B 0.291925 0.024115 AxIxR CcChH 8.3 0.5 27.6 10.629105 3.0952e−08 1.00000 B 0.300725 0.019683 PxVxK CcCcH 13.5 1.9 84.7 8.381770 4.1718e−08 1.00000 B 0.159386 0.022965 GxWxT CcEcC 9.5 0.9 21.6 9.360565 4.2598e−08 1.00000 B 0.439815 0.040902 SxGxN HcCcC 25.3 9.2 143.6 5.513759 4.5713e−08 1.00000 N 0.176184 0.063763 KxWxE CcHhH 18.1 5.5 80.6 5.559426 4.6811e−08 1.00000 N 0.224566 0.068327 HxGxI EcCcE 8.9 0.7 23.9 9.773384 4.7466e−08 1.00000 B 0.372385 0.030209 GxDxS CcChH 35.0 14.7 228.2 5.462292 4.9765e−08 1.00000 N 0.153374 0.064532 DxGxT CcChH 14.4 2.3 86.8 8.053573 5.0224e−08 1.00000 B 0.165899 0.026657 ExCxL EcCcC 7.0 0.4 14.6 10.508475 5.2940e−08 1.00000 B 0.479452 0.027746 QxLxR HhCeE 6.0 0.2 5.5 12.663540 5.3355e−08 1.00000 B 1.090909 0.033159

TABLE 15 In Expected P-Value P-Value Observed Null Sequence Structure Epitopes in Epi In PDB Z-Score Upper Lower Distribution Ratio Probability GxGKS CcCHH 76.8 5.7 258.3 30.117905 8.1947e−197 1.00000 N 0.297329 0.022063 GxGKT CcCHH 71.0 7.8 333.8 22.901721 1.4036e−114 1.00000 N 0.212702 0.023362 AxKTT CcHHH 30.3 0.5 54.5 43.761508 1.2949e−47 1.00000 B 0.555963 0.008600 DxAGK CcCCH 22.0 0.2 41.3 47.793028 8.6206e−40 1.00000 B 0.532688 0.005059 TxVDK EeEEE 90.0 25.8 396.0 13.077707 8.3835e−39 1.00000 N 0.227273 0.065121 TxTGK CcCCH 29.5 1.0 40.8 28.771739 5.4168e−38 1.00000 B 0.723039 0.024647 SxKVD CeEEE 63.6 15.5 231.4 12.646853 3.0755e−36 1.00000 N 0.274849 0.066994 SxVGK CcCCH 23.3 0.5 68.7 32.580886 2.7209e−32 1.00000 B 0.339156 0.007184 KxDKK EeEEE 72.2 22.8 341.6 10.701700 1.5998e−26 1.00000 N 0.211358 0.066796 VxCKN EcCCC 27.9 1.9 55.4 19.445212 3.8832e−26 1.00000 B 0.503610 0.033503 SxKTT CcHHH 19.7 0.5 60.3 28.032814 5.4204e−26 1.00000 B 0.326700 0.007862 GxTNS CcHHH 24.7 1.5 42.7 19.617101 6.3209e−25 1.00000 B 0.578454 0.034045 NxACK EeCCC 24.2 1.7 45.0 17.623350 9.2961e−23 1.00000 B 0.537778 0.037658 SxTKV HcEEE 63.7 20.9 316.4 9.703558 4.3917e−22 1.00000 N 0.201327 0.065941 AxIGR CcCCH 9.7 0.0 16.7 57.885963 6.0124e−22 1.00000 B 0.580838 0.001675 NxGKT CcCHH 19.3 0.9 37.9 20.057542 9.8345e−22 1.00000 B 0.509235 0.022811 SxKST CcHHH 19.2 0.8 76.4 21.405193 1.4297e−21 1.00000 B 0.251309 0.009821 QxGKT CcCHH 18.3 1.0 26.2 17.901767 1.8566e−20 1.00000 B 0.698473 0.037136 TxNIG EeCCC 15.3 0.4 13.6 20.474271 6.1792e−20 1.00000 B 1.125000 0.031424 VxKSS CcHHH 15.0 0.4 39.5 22.555376 6.7674e−20 1.00000 B 0.379747 0.010689 VxKTS CcHHH 15.5 0.4 39.6 22.701630 7.4836e−20 1.00000 B 0.391414 0.011232 GxGLG CcCHH 13.3 0.3 18.5 23.108179 1.2849e−19 1.00000 B 0.718919 0.017353 CxAGI CcCCC 10.8 0.1 24.5 35.991458 1.9508e−19 1.00000 B 0.440816 0.003628 SxTGN CcCCH 15.2 0.5 13.6 18.979056 4.1390e−19 1.00000 B 1.117647 0.036383 CxGNI EcCCC 7.0 0.0 12.0 65.388018 5.6234e−19 1.00000 B 0.583333 0.000953 AxGRT HcCCC 20.9 1.8 39.1 14.657288 6.6192e−18 1.00000 B 0.534527 0.045587 NxLFV CcCEE 2.0 0.1 2.0 6.867619 1.7331e−17 1.00000 B 1.000000 0.040680 RxTDV CcCCH 3.0 0.1 2.0 5.982392 2.2260e−17 1.00000 B 1.500000 0.052925 VxKSA CcHHH 12.4 0.3 50.8 23.682682 2.9348e−17 1.00000 B 0.244094 0.005196 YxSGR HhCCC 18.3 1.4 32.2 14.636474 6.2283e−17 1.00000 B 0.568323 0.043307 QxTYS CcCEE 1.7 0.1 1.0 3.973058 1.0441e−16 1.00000 B 1.700000 0.059576 HxASV EeEEC 3.0 0.1 1.0 4.165174 1.0497e−16 1.00000 B 3.000000 0.054500 KxVHA HcHHH 1.0 0.0 1.0 4.757945 1.0633e−16 1.00000 B 1.000000 0.042305 NxPKC CcCCC 1.0 0.0 1.0 4.879347 1.0655e−16 1.00000 B 1.000000 0.040310 SxNTY EhHHH 1.0 0.0 1.0 5.471530 1.0743e−16 1.00000 B 1.000000 0.032323 DxRFV CcCCE 1.0 0.0 1.0 5.693042 1.0770e−16 1.00000 B 1.000000 0.029931 GxRDN CcEEE 1.0 0.0 1.0 7.131346 1.0888e−16 1.00000 B 1.000000 0.019284 PxYAS CeEEC 1.0 0.0 1.0 7.330621 1.0899e−16 1.00000 B 1.000000 0.018269 NxKVD CeEEE 34.1 9.4 138.3 8.361157 1.2840e−16 1.00000 N 0.246565 0.067811 AxIGR CcCHH 7.3 0.0 20.2 44.635958 3.9779e−16 1.00000 B 0.361386 0.001316 KxVAC EeECC 17.6 1.4 42.0 14.190491 2.2162e−15 1.00000 B 0.419048 0.032245 RxSET EeCCC 13.5 0.6 32.5 16.822086 4.6601e−15 1.00000 B 0.415385 0.018436 PxSGK CcCCH 11.0 0.3 33.9 18.247326 2.6524e−14 1.00000 B 0.324484 0.010162 QxKEG HhHHC 24.5 3.8 61.1 10.933736 4.3327e−14 1.00000 B 0.400982 0.062470 QxNTN CeCCC 17.4 1.8 28.1 11.884158 5.1239e−14 1.00000 B 0.619217 0.065309 CxGDS CcCCC 15.2 0.9 207.8 14.779991 6.0370e−14 1.00000 B 0.073147 0.004503 GxTDW EeCCC 9.1 0.3 9.4 16.644901 6.1205e−14 1.00000 B 0.968085 0.030755 LxNIC CcCCC 6.0 0.0 9.0 35.855552 7.2836e−14 1.00000 B 0.666667 0.003092 MxLCT EeCCC 8.0 0.1 11.1 21.256674 1.0538e−13 1.00000 B 0.720721 0.012478 GxLAH CcCEE 12.8 0.6 32.0 15.555407 1.0819e−13 1.00000 B 0.400000 0.019525 PxWNI CeECC 12.3 0.3 9.3 16.048196 1.1558e−13 1.00000 B 1.322581 0.034852 TxCGV CcEEE 5.3 0.0 5.0 42.614482 1.5607e−13 1.00000 B 1.060000 0.002746 MxTFK HcCCC 9.5 0.3 10.7 17.091968 1.6743e−13 1.00000 B 0.887850 0.027865 TxKTF CcHHH 8.0 0.1 10.8 20.437125 1.6991e−13 1.00000 B 0.740741 0.013854 AxVGR CcCHH 8.3 0.1 21.0 23.322674 1.9270e−13 1.00000 B 0.395238 0.005887 GxICR CcCCH 5.0 0.0 10.7 51.742841 1.9290e−13 1.00000 B 0.467290 0.000870 RxLGR CcHHH 7.0 0.1 7.5 21.419092 3.3098e−13 1.00000 B 0.933333 0.014013 QxPNR HcHHH 17.2 1.8 47.4 11.863888 4.3286e−13 1.00000 B 0.362869 0.037114 AxKNG CcCCC 22.6 3.5 59.6 10.545781 4.7755e−13 1.00000 B 0.379195 0.058531 QxIMS CcHHH 5.0 0.0 5.0 36.728563 6.8672e−13 1.00000 B 1.000000 0.003693 GxVGK CcCCH 14.6 1.0 107.2 13.322350 1.6400e−12 1.00000 B 0.136194 0.009752 PxVGK CcCCH 12.0 0.6 51.9 14.216855 1.7503e−12 1.00000 B 0.231214 0.012444 SxSGK CcCCH 7.7 0.1 25.4 24.456096 1.8641e−12 1.00000 B 0.303150 0.003820 NxGKS CcCHH 12.5 0.7 33.0 13.743835 2.1757e−12 1.00000 B 0.378788 0.022670 CxGCH ChHHH 9.4 0.3 12.7 15.666301 2.1818e−12 1.00000 B 0.740157 0.027045 QxVGK CcCCH 5.0 0.0 10.0 39.581665 2.5288e−12 1.00000 B 0.500000 0.001588 SxGIG CcCCH 5.9 0.0 23.8 38.855311 3.3879e−12 1.00000 B 0.247899 0.000962 DxGVG CcCCC 17.9 2.1 85.4 11.043562 5.6770e−12 1.00000 B 0.209602 0.024576 GxTVE CeEEE 19.5 2.9 45.9 10.091362 6.2818e−12 1.00000 B 0.424837 0.062984 SxGVG CcCCH 7.7 0.1 25.5 22.270296 6.6754e−12 1.00000 B 0.301961 0.004568 HxLAV EeEEE 5.0 0.0 10.7 35.885329 7.3464e−12 1.00000 B 0.467290 0.001804 VxKSN CcHHH 6.3 0.1 11.0 25.731736 7.6458e−12 1.00000 B 0.572727 0.005376 TxAGK CcCCH 9.1 0.3 20.0 15.689912 8.4739e−12 1.00000 B 0.455000 0.015917 DxGKT CcCHH 10.5 0.5 43.6 14.602866 2.0076e−11 1.00000 B 0.240826 0.010926 NxGYH EcCCE 11.7 0.7 37.8 13.208215 2.2537e−11 1.00000 B 0.309524 0.018678 PxGPP CcCCC 18.4 2.7 56.0 9.854107 3.9241e−11 1.00000 B 0.328571 0.047758 CxSCW CeCHH 4.9 0.0 28.3 47.000314 4.6279e−11 1.00000 B 0.173145 0.000383 RxRPF EeCCC 7.5 0.2 7.0 14.155047 4.9950e−11 1.00000 B 1.071429 0.033757 NxTPN HhCHH 18.4 2.8 46.3 9.571722 5.2061e−11 1.00000 B 0.397408 0.060928 QxSGK CcCCH 8.2 0.3 19.9 15.915318 5.6650e−11 1.00000 B 0.412060 0.012692 TxKFY CcCEC 8.0 0.3 9.5 13.315750 5.8205e−11 1.00000 B 0.842105 0.036110 SxGNT CcCHH 8.0 0.3 12.7 13.715844 1.4847e−10 1.00000 B 0.629921 0.025318 CxSCW CcCHH 4.6 0.0 33.7 45.330484 1.5256e−10 1.00000 B 0.136499 0.000304 TxKTT CcHHH 10.0 0.5 49.2 12.893235 1.5785e−10 1.00000 B 0.203252 0.011055 NxGLG CcCHH 8.0 0.1 6.1 16.108152 1.6728e−10 1.00000 B 1.311475 0.022969 YxTMS CcCEE 11.7 0.8 42.8 11.916591 1.8497e−10 1.00000 B 0.273364 0.019773 FxRIL CcCCC 8.8 0.4 17.8 14.255412 1.9039e−10 1.00000 B 0.494382 0.020107 QxGSC CcCCH 7.5 0.2 20.2 17.095416 2.0620e−10 1.00000 B 0.371287 0.009148 IxNYT EcCCC 9.6 0.4 48.0 13.897106 2.2756e−10 1.00000 B 0.200000 0.009137 KxVNT CcEEE 10.5 0.6 64.8 12.844695 2.6279e−10 1.00000 B 0.162037 0.009254 PxMNR CcCCH 7.9 0.3 9.0 13.625788 2.6767e−10 1.00000 B 0.877778 0.035649 FxYSQ CcCCC 8.2 0.5 8.0 10.849473 2.6899e−10 1.00000 B 1.025000 0.063638 LxVGM CeEEE 3.5 0.0 7.0 82.843231 2.8933e−10 1.00000 B 0.500000 0.000255 AxGKT CcCHH 17.5 2.5 101.1 9.616395 2.9615e−10 1.00000 B 0.173096 0.024688 GxTGK CcCCH 8.0 0.3 35.0 14.675535 3.1693e−10 1.00000 B 0.228571 0.007972 KxNNY EeCCC 9.2 0.5 8.5 11.373392 3.3783e−10 1.00000 B 1.082353 0.061659 YxHFC CcCCC 6.0 0.2 6.0 13.955900 7.1245e−10 1.00000 B 1.000000 0.029885 QxQCG CcCCC 8.4 0.3 27.1 13.832080 7.5500e−10 1.00000 B 0.309963 0.012679 QxRGY CcCCH 7.8 0.3 9.1 13.087877 7.7131e−10 1.00000 B 0.857143 0.037102

TABLE 16 In Expected P-Value P-Value Observed Null Sequence Structure Epitopes in Epi In PDB Z-Score Upper Lower Distribution Ratio Probability SGxxT CChhH 50.1 5.4 204.2 19.480512 5.5365e−83 1.00000 N 0.245348 0.026478 YHxxN HHhhH 50.5 6.5 81.8 18.012634 3.0622e−71 1.00000 N 0.617359 0.079280 NKxxL ECccC 51.0 6.6 166.5 17.606843 3.5567e−68 1.00000 N 0.306306 0.039743 AGxxT CChhH 48.1 6.2 185.3 17.110741 2.0133e−64 1.00000 N 0.259579 0.033476 HExxH HHhhH 53.2 3.1 231.0 28.733287 2.3099e−48 1.00000 B 0.230303 0.013348 ACxxG CCccC 42.2 6.3 122.4 14.733487 3.9997e−48 1.00000 N 0.344771 0.051214 VIxxW CChhH 27.8 0.4 36.0 41.212009 5.6053e−45 1.00000 B 0.772222 0.012391 TGxxK CCccH 38.5 6.6 151.0 12.684841 4.4532e−36 1.00000 N 0.254967 0.043773 GVxxS CCchH 55.7 13.3 271.0 11.955548 1.6382e−32 1.00000 N 0.205535 0.048905 QDxxG HHhhC 41.1 8.7 96.0 11.495017 5.3755e−30 1.00000 N 0.428125 0.090888 EExxR HHhhH 314.5 174.2 1989.2 11.126843 7.2386e−29 1.00000 N 0.158104 0.087580 NFxxL HHhhH 42.8 5.0 298.3 17.058911 3.0896e−26 1.00000 B 0.143480 0.016745 VGxxS CChhH 33.7 3.0 132.7 17.980865 2.6985e−25 1.00000 B 0.253956 0.022495 LSxxE CChhH 117.4 48.7 851.8 10.137582 3.9929e−24 1.00000 N 0.137826 0.057178 FPxxL HHhhH 39.1 9.1 187.5 10.217915 4.6988e−24 1.00000 N 0.208533 0.048396 GFxxS CChhH 27.0 2.0 67.8 18.155159 5.3814e−24 1.00000 B 0.398230 0.028894 SGxxK CCccH 36.9 8.3 196.7 10.104654 1.5766e−23 1.00000 N 0.187595 0.042407 EAxxA HHhhH 202.1 104.3 2020.6 9.828707 6.9670e−23 1.00000 N 0.100020 0.051634 RRxxE HHhhH 190.5 98.6 1055.7 9.717855 2.1236e−22 1.00000 N 0.180449 0.093412 LSxxY HHhhH 44.5 11.7 344.0 9.754079 3.7941e−22 1.00000 N 0.129360 0.034022 GLxxW EEccC 12.6 0.2 19.4 30.324768 5.5134e−21 1.00000 B 0.649485 0.008738 TKxxK EEeeE 96.0 39.8 398.3 9.392073 6.4809e−21 1.00000 N 0.241024 0.099903 DExxR HHhhH 151.9 74.7 886.6 9.330064 9.3406e−21 1.00000 N 0.171329 0.084280 AAxxA HHhhH 198.7 105.9 3428.0 9.159010 4.1321e−20 1.00000 N 0.057964 0.030896 MNxxE CChhH 44.6 13.0 167.5 9.123343 1.3666e−19 1.00000 N 0.266269 0.077633 EGxxY ECccC 26.9 5.8 66.1 9.140516 2.2564e−19 1.00000 N 0.406959 0.088175 LTxxE CChhH 100.6 43.5 866.0 8.873080 7.1316e−19 1.00000 N 0.116166 0.050279 SKxxH HHhhH 34.0 8.8 105.4 8.902407 1.3189e−18 1.00000 N 0.322581 0.083153 EExxA HHhhH 231.4 135.1 1569.7 8.663887 3.3802e−18 1.00000 N 0.147417 0.086081 STxxD CEeeE 70.3 27.5 272.3 8.618319 8.1370e−18 1.00000 N 0.258171 0.100879 VSxxE CChhH 56.4 19.6 340.2 8.573591 1.3696e−17 1.00000 N 0.165785 0.057539 ARxxA HHhhH 122.1 58.7 1454.9 8.445356 2.6748e−17 1.00000 N 0.083923 0.040353 NYxxQ HHhhH 29.9 7.3 161.4 8.557089 2.9366e−17 1.00000 N 0.185254 0.045252 AAxxG HHhhC 61.5 22.3 619.8 8.471116 3.0525e−17 1.00000 N 0.099226 0.035912 PTxxI CEecC 14.3 0.7 18.8 16.909102 3.0897e−17 1.00000 B 0.760638 0.035827 AAxxR HHhhH 129.8 64.3 1242.9 8.387023 4.2884e−17 1.00000 N 0.104433 0.051739 GTxxT CCchH 27.9 6.6 168.1 8.420003 1.0007e−16 1.00000 N 0.165973 0.039491 VVxxR CCeeC 1.0 0.1 1.0 3.359317 1.0199e−16 1.00000 B 1.000000 0.081400 QQxxY HChhH 1.0 0.1 1.0 3.385522 1.0211e−16 1.00000 B 1.000000 0.080245 TQxxK CCccH 16.3 1.3 19.9 13.788693 1.7270e−16 1.00000 B 0.819095 0.063780 AAxxQ HHhhH 100.7 46.6 848.8 8.140927 3.6432e−16 1.00000 N 0.118638 0.054957 ERxxM HHhhE 17.3 1.2 36.5 14.665548 4.8047e−16 1.00000 B 0.473973 0.034006 LSxxQ CChhH 60.8 22.9 428.9 8.130612 5.1480e−16 1.00000 N 0.141758 0.053451 AExxR HHhhH 179.1 100.8 1506.8 8.070792 5.3200e−16 1.00000 N 0.118861 0.066910 PExxR HHhhH 110.7 53.8 655.7 8.086699 5.4810e−16 1.00000 N 0.168827 0.082123 RExxL HHhhH 112.2 54.5 836.4 8.083483 5.5774e−16 1.00000 N 0.134146 0.065161 VAxxN ECccC 25.5 6.1 95.8 8.160134 9.3058e−16 1.00000 N 0.266180 0.063248 NExxR HHhhH 68.6 27.9 378.6 7.995600 1.4251e−15 1.00000 N 0.181194 0.073776 RExxR HHhhH 155.0 85.2 968.1 7.921336 1.8513e−15 1.00000 N 0.160107 0.087988 SAxxG CCccH 18.0 1.4 74.6 14.080334 3.0822e−15 1.00000 B 0.241287 0.018959 QFxxN CEccC 17.6 1.6 32.4 13.170193 6.2448e−15 1.00000 B 0.543210 0.048103 GHxxL CHhhC 13.2 0.8 17.8 14.597369 6.8060e−15 1.00000 B 0.741573 0.042626 ISxxT CChhH 29.2 5.0 113.2 11.136582 6.9787e−15 1.00000 B 0.257951 0.043782 PVxxA HHhhH 42.9 14.1 430.6 7.802016 8.8311e−15 1.00000 N 0.099628 0.032730 PGxxE CChhH 48.5 17.5 230.5 7.724590 1.4791e−14 1.00000 N 0.210412 0.075770 ASxxT HCccC 23.5 5.6 109.1 7.765462 2.2008e−14 1.00000 N 0.215399 0.051334 KNxxC EEecC 16.4 1.3 42.0 13.547220 2.8206e−14 1.00000 B 0.390476 0.030577 CQxxS CCccC 22.8 5.3 160.0 7.735656 2.8522e−14 1.00000 N 0.142500 0.033098 QTxxR HChhH 18.2 1.8 48.4 12.642180 2.9192e−14 1.00000 B 0.376033 0.036274 NQxxN HHchH 21.5 5.1 47.3 7.729667 3.3269e−14 1.00000 N 0.454545 0.107054 FRxxD HHhhC 17.5 1.4 102.5 13.730817 3.4864e−14 1.00000 B 0.170732 0.013607 AAxxE HHhhH 158.9 89.7 1585.3 7.528216 3.8940e−14 1.00000 N 0.100233 0.056558 PExxA HHhhH 127.9 68.2 958.9 7.506229 4.9065e−14 1.00000 N 0.133382 0.071091 RExxA HHhhH 122.1 64.6 824.6 7.452817 7.4518e−14 1.00000 N 0.148072 0.078335 QTxxT CCchH 19.0 2.3 38.5 11.408119 7.7838e−14 1.00000 B 0.493506 0.059291 PExxN HHhhH 42.6 15.0 197.4 7.430722 1.4792e−13 1.00000 N 0.215805 0.075812 PGxxA CChhH 28.5 8.0 157.5 7.445140 1.8844e−13 1.00000 N 0.180952 0.050747 AQxxS HHhhH 50.4 19.0 360.1 7.381135 1.8871e−13 1.00000 N 0.139961 0.052899 AExxQ HHhhH 100.1 50.3 642.7 7.316766 2.1891e−13 1.00000 N 0.155749 0.078242 EDxxY HHhhH 34.2 10.8 168.1 7.391077 2.3540e−13 1.00000 N 0.203450 0.063963 LPxxV CChhH 31.7 9.5 328.1 7.313760 4.3680e−13 1.00000 N 0.096617 0.028935 GSxxT CCchH 21.7 5.2 117.5 7.361159 4.7484e−13 1.00000 N 0.184681 0.044560 GGxxK CCccH 24.6 6.4 146.1 7.326094 5.2243e−13 1.00000 N 0.168378 0.044029 QAxxD HHhhH 99.7 50.5 702.9 7.189078 5.5537e−13 1.00000 N 0.141841 0.071827 MNxxD CChhH 22.2 5.6 69.2 7.324761 6.0496e−13 1.00000 N 0.320809 0.080818 AExxA HHhhH 177.1 105.6 2016.0 7.144690 6.4810e−13 1.00000 N 0.087847 0.052392 CGxxW CEchH 10.4 0.3 41.6 17.562614 6.5688e−13 1.00000 B 0.250000 0.007964 AExxS HHhhH 69.0 30.7 525.3 7.131241 9.7365e−13 1.00000 N 0.131354 0.058394 LAxxE HHhhH 111.2 58.3 1261.6 7.088647 1.0966e−12 1.00000 N 0.088142 0.046234 YQxxL HHhhH 40.1 13.9 386.6 7.155977 1.1141e−12 1.00000 N 0.103725 0.035961 GSxxS CCchH 23.4 6.1 129.5 7.214135 1.2252e−12 1.00000 N 0.180695 0.046800 RSxxE CChhH 37.0 12.6 179.8 7.134674 1.3888e−12 1.00000 N 0.205784 0.070013 PExxT HHhhH 42.2 15.3 228.7 7.116551 1.4320e−12 1.00000 N 0.184521 0.066926 RIxxN HHhhH 31.3 9.7 211.7 7.132289 1.6125e−12 1.00000 N 0.147851 0.045594 ALxxE HHhhH 108.9 57.0 1224.1 7.032913 1.6407e−12 1.00000 N 0.088963 0.046595 STxxR HHhhH 44.8 16.8 265.4 7.068810 1.9236e−12 1.00000 N 0.168802 0.063213 SWxxG EEccC 20.9 5.0 179.2 7.166893 1.9472e−12 1.00000 N 0.116629 0.028121 LGxxI CCeeE 20.7 2.8 133.5 10.850496 2.8269e−12 1.00000 B 0.155056 0.020856 NVxxK EEccC 25.3 5.0 66.0 9.489538 2.9209e−12 1.00000 B 0.383333 0.075233 PAxxA HHhhH 81.8 39.3 821.2 6.958559 3.0611e−12 1.00000 N 0.099610 0.047803 DAxxA HHhhH 128.3 71.5 1234.0 6.928395 3.2679e−12 1.00000 N 0.103971 0.057905 WGxxC ECccC 21.1 3.0 152.1 10.567647 3.5349e−12 1.00000 B 0.138725 0.019687 ISxxE CChhH 45.1 17.1 314.7 6.975012 3.6776e−12 1.00000 N 0.143311 0.054250 RRxxA HHhhH 86.1 42.7 559.3 6.903535 4.4287e−12 1.00000 N 0.153942 0.076400 EQxxA HHhhH 117.1 64.1 862.2 6.877330 4.7983e−12 1.00000 N 0.135815 0.074365 HGxxT CChhH 15.0 1.4 57.6 11.717492 5.1305e−12 1.00000 B 0.260417 0.024021 ANxxN HHhhH 26.8 7.9 128.3 6.978653 5.4345e−12 1.00000 N 0.208885 0.061203 ARxxQ HHhhH 63.9 28.5 473.6 6.834976 8.0075e−12 1.00000 N 0.134924 0.060212 AQxxA HHhhH 97.0 50.1 1116.6 6.788691 9.3146e−12 1.00000 N 0.086871 0.044831

TABLE 17 In Expected P-Value P-Value Observed Null Sequence Structure Epitopes in Epi In PDB Z-Score Upper Lower Distribution Ratio Probability NKxDL ECcCC 51.0 4.4 116.2 22.740877 5.5464e−41 1.00000 B 0.438898 0.037599 AGxTT CChHH 30.4 0.9 60.4 31.071504 1.5187e−38 1.00000 B 0.503311 0.015139 TKxDK EEeEE 87.3 25.2 364.3 12.810007 2.7096e−37 1.00000 N 0.239638 0.069249 GVxKS CCcHH 35.9 1.9 116.9 24.813673 7.8566e−35 1.00000 B 0.307100 0.016320 STxVD CEeEE 66.1 17.9 259.0 11.784220 9.9807e−32 1.00000 N 0.255212 0.069278 GFxNS CChHH 25.7 1.3 43.2 21.484488 2.0443e−27 1.00000 B 0.594907 0.030734 TGxGK CCcCH 33.6 2.8 111.4 18.471969 3.4400e−26 1.00000 B 0.301616 0.025536 SGxGK CCcCH 32.6 2.9 157.9 17.436658 6.0866e−24 1.00000 B 0.206460 0.018664 KVxKK EEeEE 71.2 24.3 349.6 9.858861 8.8905e−23 1.00000 N 0.203661 0.069538 NVxCK EEcCC 24.2 1.7 45.0 17.590163 1.0058e−22 1.00000 B 0.537778 0.037786 TQxGK CCcCH 16.3 0.7 16.3 19.157024 2.0483e−22 1.00000 B 1.000000 0.042526 VGxSS CChHH 15.0 0.4 36.0 24.399792 5.2733e−21 1.00000 B 0.416667 0.010097 AGxGR CCcHH 13.2 0.2 54.5 30.666714 5.2900e−21 1.00000 B 0.242202 0.003318 QTxKT CCcHH 15.3 0.6 18.2 19.806546 2.0252e−20 1.00000 B 0.840659 0.031369 CGxCW CEcHH 10.1 0.1 31.8 41.150449 2.8004e−20 1.00000 B 0.317610 0.001876 ACxNG CCcCC 22.7 1.7 46.9 16.272242 5.2201e−20 1.00000 B 0.484009 0.036780 CSxGI CCcCC 10.8 0.1 24.3 38.141746 6.0931e−20 1.00000 B 0.444444 0.003262 GSxKS CCcHH 19.6 1.1 69.1 17.909474 5.1058e−19 1.00000 B 0.283647 0.015713 SGxST CChHH 19.2 1.1 78.8 17.700094 9.4319e−19 1.00000 B 0.243655 0.013505 SGxTT CChHH 19.7 1.2 60.8 17.285137 1.0837e−18 1.00000 B 0.324013 0.019270 TWxIG EEcCC 12.3 0.4 12.3 19.628460 1.2719e−18 1.00000 B 1.000000 0.030937 GTxKT CCcHH 22.0 1.7 105.1 15.901012 1.6887e−18 1.00000 B 0.209324 0.015815 YAxGR HHcCC 19.2 1.4 32.9 15.460085 2.5350e−18 1.00000 B 0.583587 0.042130 LGxSI CCeEE 12.5 0.2 38.3 25.478322 3.4342e−18 1.00000 B 0.326371 0.006089 SPxSL ECcEE 42.9 12.8 185.7 8.740430 4.1484e−18 1.00000 N 0.231018 0.068739 VGxTS CChHH 15.5 0.6 40.7 18.885040 1.3617e−17 1.00000 B 0.380835 0.015473 QFxTN CEcCC 17.3 1.1 28.1 15.703799 1.4457e−17 1.00000 B 0.615658 0.039391 GTxVV CCcHH 4.0 0.1 2.0 6.359524 1.9940e−17 1.00000 B 2.000000 0.047121 SAxIG CCcCH 7.3 0.0 20.5 53.215652 3.5180e−17 1.00000 B 0.356098 0.000914 GLxDW EEcCC 9.1 0.1 11.4 26.491413 1.0313e−16 1.00000 B 0.798246 0.010192 QQxDY HChHH 1.0 0.1 1.0 4.123152 1.0485e−16 1.00000 B 1.000000 0.055554 VVxGK CEeCC 1.0 0.1 1.0 4.267421 1.0524e−16 1.00000 B 1.000000 0.052054 QSxGA HCcCC 1.0 0.0 1.0 4.675749 1.0617e−16 1.00000 B 1.000000 0.043740 HExEN EEcCC 1.0 0.0 1.0 4.702523 1.0622e−16 1.00000 B 1.000000 0.043264 FAxKL EEeCC 1.5 0.0 1.0 4.717887 1.0625e−16 1.00000 B 1.500000 0.042995 ASxNT CEhHH 1.0 0.0 1.0 4.998624 1.0675e−16 1.00000 B 1.000000 0.038482 DMxIT HCcCC 1.0 0.0 1.0 5.018322 1.0678e−16 1.00000 B 1.000000 0.038192 YIxIH EEcCC 1.5 0.0 1.0 5.296248 1.0720e−16 1.00000 B 1.500000 0.034423 TQxHG ECcCC 2.0 0.0 1.0 6.082239 1.0810e−16 1.00000 B 2.000000 0.026320 GYxDN CCeEE 1.0 0.0 1.0 14.344343 1.1049e−16 1.00000 B 1.000000 0.004837 QDxEG HHhHC 26.0 3.7 53.3 11.934122 1.7775e−16 1.00000 B 0.487805 0.070194 DNxGK CCcCH 11.3 0.3 18.0 20.870892 2.9417e−16 1.00000 B 0.627778 0.015727 SAxVG CCcCH 8.5 0.1 20.4 35.031051 3.2861e−16 1.00000 B 0.416667 0.002855 ASxRT HCcCC 17.7 1.4 31.9 14.276988 5.1468e−16 1.00000 B 0.554859 0.042862 SSxKV HCeEE 42.6 13.8 198.0 8.026654 1.5452e−15 1.00000 N 0.215152 0.069800 GSxKT CCcHH 17.5 1.3 79.1 14.243727 8.9918e−15 1.00000 B 0.221239 0.016602 PTxNI CEeCC 14.3 0.4 10.3 16.216076 9.0764e−15 1.00000 B 1.388350 0.037693 GNxCR CCcCH 6.5 0.0 14.5 46.467091 1.1355e−14 1.00000 B 0.448276 0.001343 PNxGK CCcCH 15.0 1.0 39.3 14.390978 1.3407e−14 1.00000 B 0.381679 0.024785 GAxKT CCcHH 13.6 0.6 44.4 16.519183 1.4276e−14 1.00000 B 0.306306 0.014092 KNxAC EEeCC 16.4 1.3 42.0 13.642975 2.3347e−14 1.00000 B 0.390476 0.030201 QTxNR HChHH 17.2 1.5 46.4 12.932319 3.8897e−14 1.00000 B 0.370690 0.032756 WGxGC ECcCC 20.7 2.2 129.6 12.427477 5.4394e−14 1.00000 B 0.159722 0.017317 NAxKT CCcHH 9.3 0.2 15.1 20.147303 5.9572e−14 1.00000 B 0.615894 0.013678 CLxNI ECcCC 6.0 0.0 9.0 35.616030 7.8888e−14 1.00000 B 0.666667 0.003134 AAxKT CCcHH 9.0 0.2 19.0 20.285697 8.6402e−14 1.00000 B 0.473684 0.010026 NTxVD CEeEE 32.3 9.8 136.8 7.475662 1.3386e−13 1.00000 N 0.236111 0.071465 VGxSA CChHH 12.4 0.5 56.3 16.096540 1.7662e−13 1.00000 B 0.220249 0.009725 MExCT EEcCC 8.0 0.1 11.1 20.524084 1.8190e−13 1.00000 B 0.720721 0.013363 RMxTF HHcCC 9.5 0.3 10.7 16.898890 2.0377e−13 1.00000 B 0.887850 0.028482 QGxMS CChHH 7.0 0.1 7.0 21.093959 2.1381e−13 1.00000 B 1.000000 0.015488 VAxKN ECcCC 20.9 2.9 46.7 10.827897 2.6347e−13 1.00000 B 0.447537 0.062888 GGxGK CCcCH 18.1 1.8 107.1 12.168318 3.5653e−13 1.00000 B 0.169001 0.017001 AGxGR CCcCH 8.9 0.2 33.4 21.578870 5.4421e−13 1.00000 B 0.266467 0.004931 TNxRV CChHH 8.3 0.2 8.4 16.373784 1.1096e−12 1.00000 B 0.988095 0.029661 NQxPN HHcHH 21.5 3.4 47.3 10.210149 1.1585e−12 1.00000 B 0.454545 0.071654 IVxYT ECcCC 9.3 0.3 23.0 17.597398 1.8793e−12 1.00000 B 0.404348 0.011592 GHxAL CHhHC 9.9 0.4 12.9 14.873905 2.6141e−12 1.00000 B 0.767442 0.032551 TGxTF CChHH 8.0 0.2 9.8 16.341229 3.1327e−12 1.00000 B 0.816327 0.023619 SSxGN CCcCH 8.0 0.3 8.4 14.950912 3.5866e−12 1.00000 B 0.952381 0.032853 HNxVN HHhHH 6.0 0.1 7.0 23.122716 5.0946e−12 1.00000 B 0.857143 0.009497 DAxGK CCcCH 9.0 0.3 20.7 16.159672 5.1094e−12 1.00000 B 0.434783 0.014223 CGxCW CCcHH 6.6 0.1 35.8 27.620962 1.0933e−11 1.00000 B 0.184358 0.001570 GSxVE CEeEE 15.9 2.0 34.1 10.186491 3.2680e−11 1.00000 B 0.466276 0.058124 TFxFY CCcEC 8.0 0.3 9.5 13.808045 3.3591e−11 1.00000 B 0.842105 0.033698 QGxGL CCcCH 8.0 0.3 12.9 15.079061 3.7782e−11 1.00000 B 0.620155 0.020813 SAxIG CCcCC 11.3 0.7 34.2 12.776025 3.8879e−11 1.00000 B 0.330409 0.020540 CSxGV CCcCC 7.8 0.2 26.0 18.754611 5.5937e−11 1.00000 B 0.300000 0.006412 FMxIL CCcCC 8.8 0.3 17.0 14.990622 8.1728e−11 1.00000 B 0.517647 0.019165 STxNT CCcHH 8.0 0.3 11.6 13.939347 8.2850e−11 1.00000 B 0.689655 0.026945 GQxIM CCcHH 5.0 0.0 6.0 24.219345 1.0267e−10 1.00000 B 0.833333 0.007033 YSxMS CCcEE 11.7 0.8 42.8 12.163882 1.2625e−10 1.00000 B 0.273364 0.019069 TMxRI HHhHH 11.4 0.9 25.5 11.524995 1.5721e−10 1.00000 B 0.447059 0.033919 ACxGD CCcCC 9.1 0.4 85.9 14.278707 1.7497e−10 1.00000 B 0.105937 0.004366 QGxGK CCcCH 9.2 0.5 18.4 12.798647 2.1515e−10 1.00000 B 0.500000 0.025918 QCxSC CCcCH 5.6 0.0 20.2 26.306118 3.4094e−10 1.00000 B 0.277228 0.002213 KRxNF CCcCE 7.3 0.2 20.3 15.996806 4.8000e−10 1.00000 B 0.359606 0.009803 NGxGK CCcCH 11.0 0.8 49.0 11.320321 4.8018e−10 1.00000 B 0.224490 0.016778 QVxGY CCcCH 7.8 0.3 7.1 12.079087 5.3401e−10 1.00000 B 1.098592 0.046404 KExHP HHhCC 8.5 0.5 9.3 11.568737 5.4438e−10 1.00000 B 0.913978 0.054304 RGxGR CChHH 8.0 0.5 10.0 11.451342 7.5878e−10 1.00000 B 0.800000 0.045482 LTxWK ECcCC 6.2 0.1 10.0 16.936775 7.8155e−10 1.00000 B 0.620000 0.013013 PGxGK CCcCH 19.1 3.3 118.9 8.743858 1.0050e−09 1.00000 B 0.160639 0.028106 APxVY CCeEE 9.2 0.5 111.5 12.536420 1.6006e−09 1.00000 B 0.082511 0.004353 HHxEL EEeEC 4.4 0.0 10.4 31.598476 1.7714e−09 1.00000 B 0.423077 0.001852 NVxKS CCcHH 10.0 0.8 28.0 10.736324 1.8455e−09 1.00000 B 0.357143 0.027185 PExLT HFhHH 18.8 3.4 94.8 8.545879 2.0965e−09 1.00000 B 0.198312 0.035625 QGxCG CCcCC 10.6 0.8 49.9 11.223443 2.0978e−09 1.00000 B 0.212425 0.015591 HKxQS HFhCC 5.3 0.1 7.1 19.188490 2.1092e−09 1.00000 B 0.746479 0.010555

TABLE 18 In Expected P-Value P-Value Observed Null Sequence Structure Epitopes in Epi In PDB Z-Score Upper Lower Distribution Ratio Probability AGKxT CCHhH 45.2 1.2 109.0 40.761894 1.3250e−58 1.00000 B 0.414679 0.010817 SGKxT CCHhH 44.9 1.2 149.1 39.478589 1.6432e−55 1.00000 B 0.301140 0.008274 VGKxS CCHhH 30.5 0.4 78.0 49.113385 5.0372e−49 1.00000 B 0.391026 0.004846 TKVxK EEEeE 92.3 24.5 367.4 14.170064 3.0926e−45 1.00000 N 0.251225 0.066733 STKxD CEEeE 64.9 15.7 230.1 12.882989 1.5164e−37 1.00000 N 0.282051 0.068100 ACKxG CCCcC 34.1 2.0 46.4 23.183661 1.3729e−36 1.00000 B 0.734914 0.043173 GVGxS CCChH 36.4 2.9 125.7 19.900725 3.7374e−29 1.00000 B 0.289578 0.023075 GFTxS CCHhH 25.7 1.3 42.2 21.824769 7.8086e−28 1.00000 B 0.609005 0.030577 CSAxI CCCcC 13.3 0.1 22.7 43.660373 4.7467e−26 1.00000 B 0.585903 0.004048 KVDxK EEEeE 71.7 23.7 345.2 10.223365 2.3244e−24 1.00000 N 0.207706 0.068609 QTGxT CCChH 19.0 0.8 22.9 20.352647 2.5890e−24 1.00000 B 0.829694 0.036120 VACxN ECCcC 21.9 1.3 45.0 18.018290 2.2608e−21 1.00000 B 0.486667 0.029818 SAGxG CCCcH 15.4 0.3 53.5 25.919968 3.9071e−21 1.00000 B 0.287850 0.006351 TGTxK CCCcH 13.2 0.3 24.9 24.228491 2.1996e−19 1.00000 B 0.530120 0.011540 TQTxK CCCcH 15.3 0.6 14.3 17.434283 2.3536e−19 1.00000 B 1.069930 0.044933 SGVxK CCCcH 18.3 0.9 60.9 18.724382 3.6394e−19 1.00000 B 0.300493 0.014423 GSGxS CCChH 19.9 1.3 77.0 16.792109 3.0892e−18 1.00000 B 0.258442 0.016279 GTGxT CCChH 26.9 2.9 127.9 14.224851 3.5090e−18 1.00000 B 0.210321 0.022755 GLTxW EECcC 9.1 0.1 9.4 28.802900 3.8894e−18 1.00000 B 0.968085 0.010500 NVAxK EECcC 24.2 2.7 48.5 13.323932 1.1195e−17 1.00000 B 0.498969 0.056658 NAGxT CCChH 9.3 0.1 14.9 32.073501 1.6197e−17 1.00000 B 0.624161 0.005573 QDKxG HHHhC 27.2 3.9 57.3 12.295135 4.3110e−17 1.00000 B 0.474695 0.067418 QSPxS EECcE 30.2 7.5 200.3 8.450279 7.0338e−17 1.00000 N 0.150774 0.037434 QFNxN CECcC 17.1 1.2 28.1 14.748204 8.3663e−17 1.00000 B 0.608541 0.043159 HTFxD ECCcC 1.0 0.1 1.0 4.054249 1.0466e−16 1.00000 B 1.000000 0.057350 HIAxV EEEeC 3.0 0.1 1.0 4.139053 1.0490e−16 1.00000 B 3.000000 0.055152 NKNxE EECcC 1.5 0.0 1.0 4.392794 1.0555e−16 1.00000 B 1.500000 0.049269 KRSxA HHCcC 1.0 0.0 1.0 4.431513 1.0564e−16 1.00000 B 1.000000 0.048454 FADxL EEEcC 1.5 0.0 1.0 4.615996 1.0605e−16 1.00000 B 1.500000 0.044828 HESxN EECcC 1.0 0.0 1.0 4.763003 1.0634e−16 1.00000 B 1.000000 0.042219 DASxN CCEhH 1.0 0.0 1.0 5.499204 1.0747e−16 1.00000 B 1.000000 0.032009 EYFxE HHHcC 1.0 0.0 1.0 6.536892 1.0848e−16 1.00000 B 1.000000 0.022867 SLFxE CCHhH 1.0 0.0 1.0 8.213495 1.0940e−16 1.00000 B 1.000000 0.014607 GYRxN CCEeE 1.0 0.0 1.0 13.413602 1.1041e−16 1.00000 B 1.000000 0.005527 DNAxK CCCcH 9.3 0.1 13.0 26.378846 2.7763e−16 1.00000 B 0.715385 0.009400 SSTxV HCEeE 44.7 14.5 217.1 8.214938 3.2657e−16 1.00000 N 0.205896 0.066745 TGKxT CCHhH 13.0 0.4 60.8 19.353824 4.3808e−16 1.00000 B 0.213816 0.006992 YASxR HHCcC 17.3 1.3 31.5 14.260402 5.2564e−16 1.00000 B 0.549206 0.041639 VGKxA CCHhH 13.4 0.5 59.3 17.711339 4.4786e−15 1.00000 B 0.225970 0.008981 TKMxF CCCcC 13.9 0.9 20.0 14.318899 1.3175e−14 1.00000 B 0.695000 0.043304 DGDxQ CCCcC 26.3 4.4 66.8 10.811019 2.3355e−14 1.00000 B 0.393713 0.065788 QTPxR HCHhH 17.2 1.5 46.4 12.981638 3.4999e−14 1.00000 B 0.370690 0.032542 ASGxT HCCcC 19.7 2.2 49.7 12.173113 3.6080e−14 1.00000 B 0.396378 0.043636 TGKxF CCHhH 8.0 0.1 11.3 22.053631 6.4552e−14 1.00000 B 0.707965 0.011403 NTKxD CEEeE 32.3 9.6 139.1 7.572258 6.5452e−14 1.00000 N 0.232207 0.069229 KNVxC EEEcC 15.9 1.2 42.1 13.325318 8.2636e−14 1.00000 B 0.377672 0.029601 SWGxG EECcC 20.9 2.4 146.2 11.989083 1.2563e−13 1.00000 B 0.142955 0.016530 LGNxC CCCcC 8.0 0.1 14.5 22.390499 1.2699e−13 1.00000 B 0.551724 0.008606 GNIxR CCCcH 5.0 0.0 10.7 52.390153 1.7043e−13 1.00000 B 0.467290 0.000849 PGHxA CCHhH 11.3 0.5 18.8 15.376713 2.0088e−13 1.00000 B 0.601064 0.026934 PPGxP CCCcC 24.9 4.1 88.4 10.603352 2.3088e−13 1.00000 B 0.281674 0.045833 PTWxI CEEcC 12.3 0.4 9.3 15.254719 2.7816e−13 1.00000 B 1.322581 0.038429 AGVxR CCChH 7.8 0.1 21.6 26.565655 4.0849e−13 1.00000 B 0.361111 0.003920 GYVVxD CCCeE 6.6 0.1 6.1 26.353923 4.9686e−13 1.00000 B 1.081967 0.008706 LGFxI CCEeE 9.2 0.2 34.0 19.338446 6.4511e−13 1.00000 B 0.270588 0.006387 AAGxT CCChH 9.0 0.2 21.1 18.175548 7.2886e−13 1.00000 B 0.426540 0.011145 VGKxT CCHhH 12.0 0.6 68.6 14.806952 9.9951e−13 1.00000 B 0.174927 0.008720 GAGxT CCChH 13.6 0.9 51.8 13.538893 1.7051e−12 1.00000 B 0.262548 0.017297 GSTxE CEEeE 15.9 1.8 28.0 10.991903 2.4901e−12 1.00000 B 0.567857 0.063033 TFKxY CCCeC 9.5 0.5 9.5 12.661819 9.1849e−12 1.00000 B 1.000000 0.055941 CLGxI ECCcC 6.0 0.1 10.0 23.464775 1.4656e−11 1.00000 B 0.600000 0.006440 DAAxK CCCcH 9.0 0.3 22.0 15.053553 1.8970e−11 1.00000 B 0.409091 0.015289 GSGxT CCChH 18.5 2.5 88.2 10.388049 2.1546e−11 1.00000 B 0.209751 0.027825 LGIxI CCEeE 8.5 0.2 25.4 17.263867 2.6410e−11 1.00000 B 0.334646 0.009114 QGSxK CCCcH 7.2 0.1 14.1 18.907162 2.7340e−11 1.00000 B 0.510638 0.009986 TVNxT ECCcC 9.3 0.4 25.5 15.158694 2.7348e−11 1.00000 B 0.364706 0.013852 FMRxL CCCcC 8.8 0.3 16.8 16.058362 2.8289e−11 1.00000 B 0.523810 0.017022 DKPxY CCCcC 13.2 1.3 21.2 10.594109 3.0412e−11 1.00000 B 0.622642 0.063119 CSAxV CCCcC 7.8 0.2 23.0 19.273690 3.4354e−11 1.00000 B 0.339130 0.006882 QGKxS CCHhH 7.7 0.2 7.5 15.542889 3.4721e−11 1.00000 B 1.026667 0.030111 FPExL HHHhH 17.3 2.3 71.5 10.172199 5.1552e−11 1.00000 B 0.241958 0.031580 VSWxR EEEcC 4.3 0.0 5.3 43.831075 5.4189e−11 1.00000 B 0.811321 0.001811 ETGxS ECCcC 17.6 2.4 62.0 10.000804 6.3892e−11 1.00000 B 0.283871 0.038748 NGGxM ECCcH 8.1 0.3 11.2 14.070255 6.7783e−11 1.00000 B 0.723214 0.028125 DMNxE CCChH 9.7 0.6 12.1 12.416785 7.4545e−11 1.00000 B 0.801653 0.046907 NVGxS CCChH 10.0 0.6 26.6 12.303756 1.6309e−10 1.00000 B 0.375940 0.022460 YTPxL CCCcC 11.1 0.8 39.8 11.762389 2.0298e−10 1.00000 B 0.278894 0.019713 TGAxK CCCcH 8.1 0.3 16.4 14.066473 2.2656e−10 1.00000 B 0.493902 0.019052 GTFxC CCCcC 7.0 0.3 8.3 13.618683 3.1057e−10 1.00000 B 0.843373 0.030500 HALxV EEEeE 5.0 0.0 20.1 25.741017 3.3997e−10 1.00000 B 0.248756 0.001853 AGIxR CCChH 5.9 0.1 21.2 24.217537 3.4816e−10 1.00000 B 0.278302 0.002752 GAGxS CCChH 11.0 0.8 48.0 11.250818 5.2604e−10 1.00000 B 0.229167 0.017318 ELCxL ECCcC 7.0 0.3 9.1 13.542555 5.3172e−10 1.00000 B 0.769231 0.028045 DHGxT CCChH 7.0 0.2 29.3 15.970830 5.6202e−10 1.00000 B 0.238908 0.006257 VGKxC CCHhH 10.0 0.6 60.7 12.076594 5.7001e−10 1.00000 B 0.164745 0.010060 NQTxN HHChH 17.4 2.9 46.3 8.876430 6.1701e−10 1.00000 B 0.375810 0.061769 GGTxK CCCcH 8.0 0.3 32.5 13.907304 6.5278e−10 1.00000 B 0.246154 0.009501 GLGxS ECCeE 5.5 0.1 6.7 20.909266 8.0589e−10 1.00000 B 0.820896 0.010176 WGRxV HHHhH 7.3 0.2 26.2 15.359753 1.0620e−09 1.00000 B 0.278626 0.008189 AGIxR CCCcH 7.5 0.2 24.2 14.824604 1.6308e−09 1.00000 B 0.309917 0.010005 QCGxC CCCcH 7.1 0.2 20.2 14.323869 1.7811e−09 1.00000 B 0.351485 0.011512 SSTxN CCCcH 7.0 0.3 9.0 12.195858 2.0164e−09 1.00000 B 0.777778 0.034617 MELxT EECcC 10.0 0.8 29.5 10.706236 2.0986e−09 1.00000 B 0.338983 0.025898 QGIxS CCHhH 7.0 0.3 11.2 12.503979 3.1879e−09 1.00000 B 0.625000 0.026366 HGKxT CCHhH 7.0 0.2 38.9 14.055817 3.5464e−09 1.00000 B 0.179949 0.005994 ATNxR CCChH 9.3 0.4 7.4 10.764547 4.1930e−09 1.00000 B 1.256757 0.060028 GQGxG CCChH 8.0 0.5 14.1 11.032259 4.9378e−09 1.00000 B 0.567376 0.034108 RIVxY EECcC 10.8 1.0 25.1 9.968876 5.1361e−09 1.00000 B 0.430279 0.040063 RGLxR CCHhH 7.0 0.3 10.7 11.925372 5.1481e−09 1.00000 B 0.654206 0.030208

TABLE 19 In Expected P-Value P-Value Observed Null Sequence Structure Epitopes in Epi In PDB Z-Score Upper Lower Distribution Ratio Probability AGKTT CCHHH 30.3 0.2 53.3 60.465312 5.5259e−56 1.00000 B 0.568480 0.004656 TKVDK EEEEE 86.3 20.3 363.4 15.071953 6.9306e−51 1.00000 N 0.237479 0.055879 STKVD CEEEE 61.6 13.0 230.1 13.904790 2.1619e−43 1.00000 N 0.267710 0.056344 GVGKS CCCHH 34.9 1.2 109.6 31.386429 1.1635e−40 1.00000 B 0.318431 0.010653 KVDKK EEEEE 71.2 19.4 341.6 12.131059 1.4989e−33 1.00000 N 0.208431 0.056672 CSAGI CCCCC 10.8 0.0 21.7 119.020953 6.6042e−30 1.00000 B 0.497696 0.000379 SGKST CCHHH 19.2 0.4 74.8 29.140926 2.5218e−26 1.00000 B 0.256684 0.005585 GFTNS CCHHH 24.7 1.3 41.2 20.894474 2.9243e−26 1.00000 B 0.599515 0.031442 VGKSS CCHHH 15.0 0.2 36.0 36.980645 3.1208e−26 1.00000 B 0.416667 0.004492 SGKTT CCHHH 19.7 0.5 60.8 27.874101 6.8319e−26 1.00000 B 0.324013 0.007883 GSGKS CCCHH 19.6 0.6 66.7 25.190609 3.6713e−24 1.00000 B 0.293853 0.008626 SGVGK CCCCH 18.3 0.5 53.4 25.703105 6.9392e−24 1.00000 B 0.342697 0.009079 NVACK EECCC 24.2 1.6 45.0 18.282352 1.9905e−23 1.00000 B 0.537778 0.035242 VGKTS CCHHH 15.5 0.3 39.7 29.802692 3.1710e−23 1.00000 B 0.390428 0.006628 DNAGK CCCCH 9.3 0.0 13.0 51.914426 1.6236e−21 1.00000 B 0.715385 0.002458 NAGKT CCCHH 9.3 0.0 13.9 52.186777 2.0505e−21 1.00000 B 0.669065 0.002274 GTGKT CCCHH 22.0 1.3 99.0 18.387859 6.8722e−21 1.00000 B 0.222222 0.012987 SSTKV HCEEE 41.4 11.0 198.1 9.427547 9.0951e−21 1.00000 N 0.208985 0.055556 QTGKT CCCHH 15.3 0.6 18.2 20.141893 1.2540e−20 1.00000 B 0.840659 0.030377 TQTGK CCCCH 15.3 0.6 14.3 18.234366 7.0811e−20 1.00000 B 1.069930 0.041235 AGIGR CCCCH 7.5 0.0 16.7 77.399169 1.4536e−19 1.00000 B 0.449102 0.000561 VACKN ECCCC 20.9 1.5 43.0 16.412549 2.2938e−19 1.00000 B 0.486047 0.033792 ACKNG CCCCC 21.6 1.7 43.0 15.804325 3.8946e−19 1.00000 B 0.502326 0.038517 NTKVD CEEEE 32.3 7.8 136.3 9.001505 5.8508e−19 1.00000 N 0.236977 0.057495 VGKSA CCHHH 12.4 0.2 44.0 27.218777 9.6246e−19 1.00000 B 0.281818 0.004586 TGTGK CCCCH 13.2 0.3 23.9 22.531929 1.1028e−18 1.00000 B 0.552301 0.013841 CSAGV CCCCC 6.8 0.0 21.0 90.676937 3.9652e−18 1.00000 B 0.323810 0.000267 GLTDW EECCC 9.1 0.1 9.4 28.126064 5.9368e−18 1.00000 B 0.968085 0.011006 YASGR HHCCC 17.3 1.1 30.0 16.136826 9.8425e−18 1.00000 B 0.576667 0.035026 TDVVG CCHHH 2.0 0.0 2.0 9.169227 1.0079e−17 1.00000 B 1.000000 0.023236 GTDVV CCCHH 4.0 0.1 2.0 6.652325 1.8372e−17 1.00000 B 2.000000 0.043240 ASGRT HCCCC 17.7 1.1 31.9 15.804729 2.5121e−17 1.00000 B 0.554859 0.035695 AAGKT CCCHH 9.0 0.1 19.0 32.243836 2.5944e−17 1.00000 B 0.473684 0.004047 GAGKT CCCHH 13.6 0.4 44.3 21.167039 3.8339e−17 1.00000 B 0.306998 0.008867 QSTYS CCCEE 1.3 0.1 1.0 4.271212 1.0525e−16 1.00000 B 1.300000 0.051966 IASVA EEECC 3.0 0.1 1.0 4.319109 1.0537e−16 1.00000 B 3.000000 0.050878 HTFID ECCCC 1.0 0.0 1.0 4.414173 1.0560e−16 1.00000 B 1.000000 0.048816 HIASV EEEEC 3.0 0.0 1.0 4.435998 1.0565e−16 1.00000 B 3.000000 0.048360 SRTGT CCCCC 1.0 0.0 1.0 4.483287 1.0576e−16 1.00000 B 1.000000 0.047394 PSLPT CCCCC 1.0 0.0 1.0 4.729112 1.0627e−16 1.00000 B 1.000000 0.042800 FADKL EEECC 1.5 0.0 1.0 4.930669 1.0664e−16 1.00000 B 1.500000 0.039508 HESEN EECCC 1.0 0.0 1.0 4.970215 1.0670e−16 1.00000 B 1.000000 0.038906 GTMKP CCCCC 1.7 0.0 1.0 5.689319 1.0770e−16 1.00000 B 1.700000 0.029969 TQQHG ECCCC 2.0 0.0 1.0 6.095078 1.0811e−16 1.00000 B 2.000000 0.026212 YIKIH EECCC 1.5 0.0 1.0 6.298304 1.0829e−16 1.00000 B 1.500000 0.024589 ITTLD EEEEE 1.0 0.0 1.0 6.443160 1.0841e−16 1.00000 B 1.000000 0.023521 NALAS CCCCC 1.0 0.0 1.0 7.078294 1.0885e−16 1.00000 B 1.000000 0.019569 RGFSG CCECC 1.0 0.0 1.0 7.563653 1.0911e−16 1.00000 B 1.000000 0.017180 SLFLE CCHHH 1.0 0.0 1.0 8.389016 1.0947e−16 1.00000 B 1.000000 0.014010 GYRDN CCEEE 1.0 0.0 1.0 12.986148 1.1037e−16 1.00000 B 1.000000 0.005895 QFNTN CECCC 16.8 1.1 28.1 15.369429 1.1857e−16 1.00000 B 0.597865 0.038692 DAAGK CCCCH 9.0 0.1 20.1 29.526979 1.4194e−16 1.00000 B 0.447761 0.004549 LGNIC CCCCC 6.0 0.0 9.0 57.956075 2.3546e−16 1.00000 B 0.666667 0.001188 CLGNI ECCCC 6.0 0.0 9.0 55.536718 3.9218e−16 1.00000 B 0.666667 0.001294 PPGPP CCCCC 16.8 1.2 31.0 14.517116 1.0146e−15 1.00000 B 0.541935 0.038746 GNICR CCCCH 5.0 0.0 10.7 86.957797 1.0862e−15 1.00000 B 0.467290 0.000309 QDKEG HHHHC 23.5 3.0 53.3 12.128908 1.5706e−15 1.00000 B 0.440901 0.056696 AGVGR CCCHH 7.3 0.0 20.1 39.450567 2.1921e−15 1.00000 B 0.363184 0.001691 HALAV EEEEE 5.0 0.0 7.7 68.668141 6.5384e−15 1.00000 B 0.649351 0.000688 NVGKS CCCHH 10.0 0.2 23.0 20.863516 7.0957e−15 1.00000 B 0.434783 0.009643 SAGIG CCCCH 5.9 0.0 20.5 70.678886 8.0219e−15 1.00000 B 0.287805 0.000339 TGKTF CCHHH 8.0 0.1 9.8 23.661871 9.8853e−15 1.00000 B 0.816327 0.011470 GSGKT CCCHH 16.5 1.1 77.1 14.568931 1.4235e−14 1.00000 B 0.214008 0.014651 QTPNR HCHHH 17.2 1.5 46.4 13.229385 2.0671e−14 1.00000 B 0.370690 0.031495 SAGVG CCCCH 7.5 0.0 20.4 33.668542 2.0857e−14 1.00000 B 0.367647 0.002407 GSTVE CEEEE 15.9 1.4 24.4 12.865137 2.1829e−14 1.00000 B 0.651639 0.055473 AGIGR CCCHH 5.9 0.0 20.2 61.060994 3.4266e−14 1.00000 B 0.292079 0.000461 MELCT EECCC 8.0 0.1 11.1 21.886741 6.6835e−14 1.00000 B 0.720721 0.011785 KNVAC EEECC 15.9 1.2 42.1 13.367493 7.6225e−14 1.00000 B 0.377672 0.029438 ACNGD CCCCC 5.0 0.0 6.0 48.691508 9.9218e−14 1.00000 B 0.833333 0.001753 RGLGR CCHHH 7.0 0.1 7.0 21.735542 1.4144e−13 1.00000 B 1.000000 0.014601 TWNIG EECCC 12.3 0.3 9.3 15.690258 1.7089e−13 1.00000 B 1.322581 0.036401 PTWNI CEECC 12.3 0.3 9.3 15.586625 1.9168e−13 1.00000 B 1.322581 0.036869 GGTGK CCCCH 8.0 0.1 32.0 22.161607 5.8435e−13 1.00000 B 0.250000 0.003960 VGKSN CCHHH 6.3 0.0 11.0 31.650387 6.5990e−13 1.00000 B 0.572727 0.003570 GAGKS CCCHH 9.0 0.2 22.4 18.251205 7.6963e−13 1.00000 B 0.401786 0.010409 TGAGK CCCCH 8.1 0.2 15.0 19.304260 1.5160e−12 1.00000 B 0.540000 0.011377 QGIMS CCHHH 5.0 0.0 5.0 33.817618 1.5630e−12 1.00000 B 1.000000 0.004353 DHGKT CCCHH 7.0 0.1 29.2 24.300680 2.0219e−12 1.00000 B 0.239726 0.002784 IVNYT ECCCC 9.3 0.3 22.0 17.173156 2.6007e−12 1.00000 B 0.422727 0.012703 TGKTT CCHHH 10.0 0.4 49.2 15.782827 4.3075e−12 1.00000 B 0.203252 0.007617 FMRIL CCCCC 8.8 0.2 15.0 17.816749 4.4112e−12 1.00000 B 0.586667 0.015652 VGKST CCHHH 9.7 0.3 41.3 17.282948 5.1363e−12 1.00000 B 0.234867 0.007218 PNVGK CCCCH 8.5 0.2 24.0 17.650727 1.7561e−11 1.00000 B 0.354167 0.009250 TFKFY CCCEC 8.0 0.3 9.5 14.144154 2.3311e−11 1.00000 B 0.842105 0.032186 SAGIG CCCCC 7.8 0.2 18.3 19.277002 2.5815e−11 1.00000 B 0.426230 0.008662 SPSSL ECCEE 22.6 6.2 113.2 6.737919 3.2449e−11 1.00000 N 0.199647 0.055120 AGKST CCHHH 8.6 0.3 24.6 16.358492 5.5030e−11 1.00000 B 0.349593 0.010673 NQTPN HHCHH 17.4 2.5 46.3 9.807330 5.7989e−11 1.00000 B 0.375810 0.052976 AGKTS CCHHH 4.6 0.0 6.5 45.221979 5.9445e−11 1.00000 B 0.707692 0.001587 QGSGK CCCCH 7.2 0.2 12.9 17.266587 7.6089e−11 1.00000 B 0.558140 0.013027 STGNT CCCHH 8.0 0.3 11.6 13.943602 8.2471e−11 1.00000 B 0.689655 0.026930 HGKTT CCHHH 7.0 0.1 35.2 18.613204 8.4185e−11 1.00000 B 0.198864 0.003878 SGSGK CCCCH 6.7 0.1 22.8 22.484912 8.4213e−11 1.00000 B 0.293860 0.003809 GQGIM CCCHH 5.0 0.0 5.0 22.627078 8.4618e−11 1.00000 B 1.000000 0.009671 YSTMS CCCEE 11.7 0.8 42.8 12.014476 1.5892e−10 1.00000 B 0.273364 0.019490 QTGTG CCCCC 7.5 0.2 10.0 15.134947 2.3135e−10 1.00000 B 0.750000 0.023592 VSWGR EEECC 4.3 0.0 5.3 36.339637 2.4138e−10 1.00000 B 0.811321 0.002632 FTVAQ CCHHH 7.1 0.2 15.0 16.089718 2.4804e−10 1.00000 B 0.473333 0.012462

TABLE 20 In Expected P-Value P-Value Observed Null Sequence Structure Epitopes in Epi In PDB Z-Score Upper Lower Distribution Ratio Probability LxxxxR CchhhH 243.0 57.8 1351.9 24.885394 2.8521e−136 1.00000 N 0.179747 0.042782 GxxxxQ CcchhH 255.1 81.2 1223.1 19.980536 1.2830e−88 1.00000 N 0.208568 0.066361 LxxxxQ CchhhH 126.4 29.8 922.6 18.007172 4.5848e−72 1.00000 N 0.137004 0.032258 LxxxxK CchhhH 149.3 41.7 947.4 17.047502 7.0481e−65 1.00000 N 0.157589 0.043999 GxxxxE CcchhH 400.5 186.8 2725.7 16.199779 4.6835e−59 1.00000 N 0.146935 0.068536 LxxxxM CchhhH 61.6 11.4 519.7 15.057313 1.4748e−50 1.00000 N 0.118530 0.021888 GxxxxT CcchhH 210.7 80.5 1540.2 14.898100 3.9858e−50 1.00000 N 0.136800 0.052292 LxxxxI CchhhH 120.9 37.9 1893.1 13.610400 5.3167e−42 1.00000 N 0.063864 0.020034 AxxxxV HhhhcC 87.4 23.0 1099.8 13.589463 9.7121e−42 1.00000 N 0.079469 0.020879 ExxxxW CcchhH 36.1 5.3 134.0 13.677958 1.4188e−41 1.00000 N 0.269403 0.039434 IxxxxR CchhhH 79.2 20.1 469.1 13.463888 5.9268e−41 1.00000 N 0.168834 0.042888 SxxxxR CchhhH 124.8 41.7 647.7 13.306610 3.0825e−40 1.00000 N 0.192682 0.064369 AxxxxR CchhhH 115.3 37.0 706.6 13.228266 9.2344e−40 1.00000 N 0.163176 0.052343 AxxxxI HhhhcC 71.2 17.1 836.7 13.234870 1.3942e−39 1.00000 N 0.085096 0.020406 ExxxxR EecceE 59.1 13.4 159.8 13.057590 1.8573e−38 1.00000 N 0.369837 0.083731 RxxxxE HhhccC 173.9 70.9 874.0 12.761204 2.9847e−37 1.00000 N 0.198970 0.081120 SxxxxQ CchhhH 107.1 34.6 557.3 12.734676 5.8204e−37 1.00000 N 0.192177 0.062044 NxxxxE CcchhH 188.1 80.7 1090.7 12.430866 1.8292e−35 1.00000 N 0.172458 0.073955 GxxxxS CcchhH 154.1 60.6 1208.3 12.329694 7.0867e−35 1.00000 N 0.127535 0.050132 LxxxxL CchhhH 154.3 60.1 2989.1 12.264411 1.5679e−34 1.00000 N 0.051621 0.020122 TxxxxR CchhhH 97.2 31.2 509.4 12.189503 5.4680e−34 1.00000 N 0.190813 0.061279 SxxxxR ChhhhH 261.0 129.5 1853.7 11.982428 3.8015e−33 1.00000 N 0.140799 0.069857 FxxxxR CchhhH 53.8 12.6 341.3 11.807882 9.6778e−32 1.00000 N 0.157633 0.036994 SxxxxE CcchhH 192.1 88.4 1305.4 11.424853 2.9571e−30 1.00000 N 0.147158 0.067710 VxxxxF CcchhH 39.3 7.9 319.7 11.295066 5.2957e−29 1.00000 N 0.122928 0.024762 FxxxxE EcchhH 34.0 6.3 182.6 11.217448 1.6197e−28 1.00000 N 0.186199 0.034562 GxxxxD CcchhH 262.4 137.5 2156.0 11.007428 2.8665e−28 1.00000 N 0.121707 0.063779 TxxxxT EecceE 82.4 27.3 361.9 10.952964 9.5962e−28 1.00000 N 0.227687 0.075539 TxxxxE CcchhH 153.7 67.3 1094.5 10.868932 1.6117e−27 1.00000 N 0.140429 0.061501 KxxxxW EecceE 36.7 7.5 127.6 10.966382 2.1756e−27 1.00000 N 0.287618 0.058953 DxxxxR CchhhH 136.7 58.0 811.5 10.718357 8.6960e−27 1.00000 N 0.168453 0.071505 YxxxxE CcchhH 85.7 29.3 538.1 10.711761 1.2450e−26 1.00000 N 0.159264 0.054469 LxxxxI HhhccC 81.5 26.8 1641.0 10.661368 2.1892e−26 1.00000 N 0.049665 0.016319 RxxxxF EeeccC 48.1 12.1 197.8 10.669917 3.4327e−26 1.00000 N 0.243175 0.061253 KxxxxY EecceE 31.7 6.0 126.7 10.691459 5.1661e−26 1.00000 N 0.250197 0.047719 GxxxxR CchhhH 118.7 48.8 850.2 10.297931 7.7223e−25 1.00000 N 0.139614 0.057438 GxxxxR CcchhH 133.1 57.9 856.2 10.244740 1.2603e−24 1.00000 N 0.155454 0.067572 ExxxxE CcchhH 191.6 95.5 1299.3 10.213154 1.4953e−24 1.00000 N 0.147464 0.073517 GxxxxN CcchhH 104.6 41.2 673.7 10.207393 2.0976e−24 1.00000 N 0.155262 0.061083 QxxxxT EecceE 35.6 7.8 134.6 10.298441 2.4065e−24 1.00000 N 0.264487 0.057628 VxxxxQ EchhhC 23.8 1.4 40.9 19.211871 4.9634e−24 1.00000 B 0.581907 0.034401 RxxxxD HhhccC 174.6 85.9 1073.5 9.970399 1.8063e−23 1.00000 N 0.162646 0.080061 FxxxxE CcchhH 87.8 32.5 685.4 9.926259 3.9216e−23 1.00000 N 0.128100 0.047474 LxxxxV CchhhH 90.3 33.8 1719.7 9.813784 1.1574e−22 1.00000 N 0.052509 0.019657 RxxxxH HhhccC 65.2 21.7 297.8 9.703437 4.3224e−22 1.00000 N 0.218939 0.072826 GxxxxY CcchhH 68.3 23.1 533.9 9.630341 8.3399e−22 1.00000 N 0.127927 0.043196 AxxxxE CcchhH 148.0 70.1 1242.5 9.573740 9.3271e−22 1.00000 N 0.119115 0.056438 WxxxxR CchhhH 33.4 7.5 151.7 9.659593 1.3620e−21 1.00000 N 0.220171 0.049712 DxxxxT EccccE 70.6 24.4 581.0 9.569481 1.4539e−21 1.00000 N 0.121515 0.041937 PxxxxQ CcchhH 109.4 46.5 1083.7 9.421620 4.5216e−21 1.00000 N 0.100950 0.042935 DxxxxR ChhhhH 237.0 133.2 1783.5 9.344319 7.0694e−21 1.00000 N 0.132885 0.074710 GxxxxK CcchhH 153.6 75.4 1023.0 9.348950 7.7771e−21 1.00000 N 0.150147 0.073750 TxxxxR ChhhhH 192.4 101.8 1444.8 9.314664 9.9140e−21 1.00000 N 0.133167 0.070455 RxxxxQ CcchhH 80.6 30.6 502.4 9.316053 1.4468e−20 1.00000 N 0.160430 0.060976 YxxxxG EecccC 128.5 59.1 1454.7 9.226183 2.6007e−20 1.00000 N 0.088334 0.040595 QxxxxE CcchhH 111.8 49.3 708.3 9.233590 2.6009e−20 1.00000 N 0.157843 0.069571 DxxxxE CcchhH 154.5 77.4 1117.3 9.079327 9.3679e−20 1.00000 N 0.138280 0.069298 FxxxxY CchhhC 30.2 6.8 172.7 9.178860 1.3184e−19 1.00000 N 0.174870 0.039245 ExxxxS HhhccC 134.5 64.7 919.1 8.999618 2.0332e−19 1.00000 N 0.146339 0.070398 NxxxxR CchhhH 74.6 28.5 442.8 8.941105 4.6087e−19 1.00000 N 0.168473 0.064272 QxxxxL EecceE 42.9 12.1 459.9 8.967760 5.6147e−19 1.00000 N 0.093281 0.026328 ExxxxV EcceeE 46.8 14.0 318.4 8.939876 6.6359e−19 1.00000 N 0.146985 0.044109 VxxxxR EchhhC 25.4 2.5 69.9 14.588668 8.5240e−19 1.00000 B 0.363376 0.036434 ExxxxK HchhhH 29.4 6.9 82.3 8.942929 1.1236e−18 1.00000 N 0.357230 0.083914 DxxxxQ ChhhhH 152.3 77.8 1117.8 8.751110 1.7751e−18 1.00000 N 0.136250 0.069630 KxxxxY HhhccC 67.0 24.7 384.0 8.786447 1.9357e−18 1.00000 N 0.174479 0.064410 ExxxxL EecceE 40.3 11.3 277.3 8.826998 2.0686e−18 1.00000 N 0.145330 0.040651 CxxxxY EecccC 27.4 3.0 127.4 14.220807 2.5238e−18 1.00000 B 0.215071 0.023644 PxxxxR CchhhH 112.2 51.7 866.2 8.685640 3.5307e−18 1.00000 N 0.129531 0.059641 GxxxxQ CchhhH 65.4 23.9 462.5 8.714553 3.6676e−18 1.00000 N 0.141405 0.051690 GxxxxQ CcehhH 28.4 6.7 87.1 8.747114 6.3844e−18 1.00000 N 0.326062 0.076678 NxxxxK CchhhH 81.3 33.5 456.0 8.591494 9.3418e−18 1.00000 N 0.178289 0.073378 YxxxxH CccccE 25.8 5.6 128.0 8.709907 9.9702e−18 1.00000 N 0.201563 0.043878 ExxxxK EcceeE 43.1 13.1 168.8 8.606301 1.3067e−17 1.00000 N 0.255332 0.077849 LxxxxE CcchhH 116.0 54.7 1020.9 8.516601 1.4929e−17 1.00000 N 0.113625 0.053595 ExxxxR CchhhH 96.4 42.8 631.6 8.492481 1.9932e−17 1.00000 N 0.152628 0.067721 ExxxxR EcceeE 39.2 11.5 139.1 8.542044 2.4730e−17 1.00000 N 0.281812 0.082523 IxxxxL CchhhH 79.6 32.1 1654.6 8.474998 2.5182e−17 1.00000 N 0.048108 0.019383 SxxxxQ CcchhH 97.8 43.8 663.1 8.432856 3.2796e−17 1.00000 N 0.147489 0.066115 KxxxxN HhhccC 132.1 66.5 806.8 8.389233 4.2077e−17 1.00000 N 0.163733 0.082483 ExxxxR HhhccC 116.1 55.9 742.2 8.375368 4.9567e−17 1.00000 N 0.156427 0.075303 HxxxxR CchhhH 42.2 12.9 198.2 8.441254 5.3279e−17 1.00000 N 0.212916 0.065049 MxxxxR CchhhH 51.3 17.3 353.0 8.401305 6.2683e−17 1.00000 N 0.145326 0.048896 WxxxxK HhhhcC 38.8 11.2 266.7 8.429782 6.3105e−17 1.00000 N 0.145482 0.041973 GxxxxF EecceE 33.3 8.7 334.0 8.436510 6.9899e−17 1.00000 N 0.099701 0.026101 VxxxxR CchhhH 75.7 30.6 650.5 8.356763 7.0348e−17 1.00000 N 0.116372 0.047016 VxxxxF CchhhH 40.9 12.1 688.2 8.383240 8.7602e−17 1.00000 N 0.059430 0.017513 RxxxxR HhhhhH 509.6 359.0 4907.4 8.254956 9.5544e−17 1.00000 N 0.103843 0.073158 SxxxxQ ChhhhH 176.9 97.8 1537.4 8.267115 1.0620e−16 1.00000 N 0.115064 0.063607 VxxxxE EcchhH 59.9 21.9 499.1 8.298175 1.3176e−16 1.00000 N 0.120016 0.043910 GxxxxA CcchhH 152.0 80.0 1799.4 8.235044 1.4447e−16 1.00000 N 0.084473 0.044459 RxxxxE EecceE 36.6 10.6 131.4 8.302230 1.9387e−16 1.00000 N 0.278539 0.080969 IxxxxY EcceeE 25.5 5.7 229.8 8.350186 1.9949e−16 1.00000 N 0.110966 0.024988 YxxxxQ EccccC 41.7 12.9 277.2 8.238435 2.8485e−16 1.00000 N 0.150433 0.046375 KxxxxE CcchhH 180.8 102.1 1300.8 8.119417 3.5770e−16 1.00000 N 0.138991 0.078458 RxxxxL HhhccC 95.2 43.3 774.6 8.128103 4.1443e−16 1.00000 N 0.122902 0.055843 ExxxxY EcceeE 29.7 7.7 170.1 8.125602 1.0025e−15 1.00000 N 0.174603 0.045189 ExxxxD HhhheC 18.8 1.6 44.9 13.980628 1.0075e−15 1.00000 B 0.418708 0.035042 QxxxxQ CchhhH 45.1 15.0 238.9 8.045709 1.2643e−15 1.00000 N 0.188782 0.062644

TABLE 21 In Expected P-Value P-Value Observed Null Sequence Structure Epitopes in Epi In PDB Z-Score Upper Lower Distribution Ratio Probability VxxxNF CcchHH 23.5 0.1 36.1 60.676785 1.6831e−46 1.00000 B 0.650970 0.004120 TxxxKT CcccHH 42.4 3.9 131.3 19.889388 9.5748e−32 1.00000 B 0.322925 0.029453 AxxxGV HhhhCC 45.2 9.8 582.5 11.387117 1.5163e−29 1.00000 N 0.077597 0.016857 ExxxMD HhhhEC 16.7 0.2 36.2 35.393181 6.7544e−27 1.00000 B 0.461326 0.006027 GxxxST CcchHH 41.3 9.3 215.2 10.727154 2.2945e−26 1.00000 N 0.191914 0.043218 GxxxTT CcchHH 45.0 10.8 228.6 10.664870 3.9274e−26 1.00000 N 0.196850 0.047226 LxxxGK CcccCH 29.0 1.9 120.0 20.108167 4.1285e−26 1.00000 B 0.241667 0.015428 SxxxDK CeeeEE 60.1 17.8 256.6 10.374931 5.7844e−25 1.00000 N 0.234217 0.069505 PxxxIG CeecCC 14.3 0.2 13.4 29.692131 3.6368e−24 1.00000 B 1.067164 0.014972 SxxxKS CcccHH 28.0 5.2 140.5 10.214096 8.4052e−24 1.00000 N 0.199288 0.036881 LxxxVM CchhHH 23.7 1.4 59.7 19.223495 6.7876e−23 1.00000 B 0.396985 0.023116 VxxxNG EcccCC 29.1 5.8 121.9 9.970960 8.5736e−23 1.00000 N 0.238720 0.047201 DxxxGK CcccCH 35.1 4.2 204.5 15.193499 9.8658e−22 1.00000 B 0.171638 0.020627 YxxxNE HhhhHH 27.3 5.5 107.9 9.499449 8.3765e−21 1.00000 N 0.253012 0.051287 DxxxKT CcccHH 24.5 2.0 64.1 15.998384 4.4565e−20 1.00000 B 0.382215 0.031767 QxxxLG CcccHH 18.4 0.9 36.3 18.490167 7.6666e−20 1.00000 B 0.506887 0.025267 QxxxWY HhhhHC 11.5 0.3 11.1 20.996615 2.3636e−18 1.00000 B 1.036036 0.024560 YxxxFQ CcccCC 18.6 1.1 41.8 16.836828 3.0671e−18 1.00000 B 0.444976 0.026523 AxxxGI HhhhCC 29.9 6.9 432.7 8.779901 4.3999e−18 1.00000 N 0.069101 0.016053 CxxxIC EcccCC 7.0 0.0 12.0 50.227535 2.2267e−17 1.00000 B 0.583333 0.001612 TxxxKK EeeeEE 69.9 27.5 416.3 8.363251 7.0078e−17 1.00000 N 0.167908 0.066081 MxxxDA HhccCH 1.0 0.0 1.0 5.293417 1.0720e−16 1.00000 B 1.000000 0.034459 QxxxSL EeccEE 27.9 6.7 256.2 8.321559 2.2276e−16 1.00000 N 0.108899 0.026065 LxxxYH HhhhHH 29.3 4.2 149.9 12.332883 2.6305e−16 1.00000 B 0.195464 0.028332 RxxxPE HhhcCC 28.5 7.2 111.5 8.193404 6.1741e−16 1.00000 N 0.255605 0.064712 QxxxGS CcccEC 11.5 0.3 38.4 20.426447 4.2192e−15 1.00000 B 0.299479 0.007887 WxxxFT HhhcCC 9.4 0.2 17.9 23.668916 6.5801e−15 1.00000 B 0.525140 0.008599 SxxxGR CcccHH 15.8 1.0 67.1 15.237596 9.2692e−15 1.00000 B 0.235469 0.014337 NxxxGK CcccCH 16.9 1.3 53.7 14.061590 1.1001e−14 1.00000 B 0.314711 0.023575 NxxxQF CcccCE 17.8 1.5 51.1 13.545332 1.1983e−14 1.00000 B 0.348337 0.029216 YxxxRT HhccCC 18.3 1.9 47.4 12.329519 5.9076e−14 1.00000 B 0.386076 0.039072 SxxxVD HceeEE 58.7 23.5 333.5 7.513806 6.4629e−14 1.00000 N 0.176012 0.070611 ExxxAE HhhhHH 82.6 37.8 768.2 7.460296 8.0982e−14 1.00000 N 0.107524 0.049269 KxxxLD HhccCC 25.2 6.4 158.0 7.548711 1.0095e−13 1.00000 N 0.159494 0.040754 KxxxCK EeecCC 17.6 1.7 48.7 12.382741 1.5752e−13 1.00000 B 0.361396 0.035054 CxxxYR HhhhHC 10.0 0.4 12.5 15.304518 1.7261e−13 1.00000 B 0.800000 0.032492 RxxxGL HhhhCC 28.6 8.1 176.7 7.393568 2.7275e−13 1.00000 N 0.161856 0.045701 QxxxCW CcccHH 7.9 0.1 20.2 25.982292 3.1500e−13 1.00000 B 0.391089 0.004492 AxxxGK CcccCH 14.4 1.0 93.3 13.642109 8.6294e−13 1.00000 B 0.154341 0.010485 ExxxAL HhhhHC 32.2 10.0 257.3 7.160501 1.2869e−12 1.00000 N 0.125146 0.038867 PxxxSA CceeEE 21.1 5.1 180.5 7.181197 1.7416e−12 1.00000 N 0.116898 0.028284 DxxxNG CcccCC 41.8 14.9 391.2 7.084546 1.7924e−12 1.00000 N 0.106851 0.038196 GxxxSA CcchHH 24.6 6.6 185.4 7.117102 2.2711e−12 1.00000 N 0.132686 0.035702 RxxxDS HhheCC 16.7 1.8 45.2 11.428338 2.6297e−12 1.00000 B 0.369469 0.039275 SxxxNT CcccHH 12.5 0.8 23.9 12.925110 3.2732e−12 1.00000 B 0.523013 0.035277 QxxxGK CcccCH 13.5 0.9 58.5 13.107957 4.1790e−12 1.00000 B 0.230769 0.015965 RxxxTG EeccCC 24.8 6.9 127.8 7.018198 4.4794e−12 1.00000 N 0.194053 0.053883 GxxxDF EeccEE 25.3 7.0 248.3 6.995039 5.0997e−12 1.00000 N 0.101893 0.028291 DxxxGS HhhhCC 20.9 3.3 65.1 9.930092 8.3751e−12 1.00000 B 0.321045 0.050797 CxxxVG CcccCH 6.8 0.1 20.0 26.127329 1.0463e−11 1.00000 B 0.340000 0.003332 SxxxGC EeccCC 15.3 1.4 138.8 11.769743 1.3088e−11 1.00000 B 0.110231 0.010141 VxxxCI HhccCH 4.0 0.0 6.5 53.088891 1.3520e−11 1.00000 B 0.615385 0.000872 ExxxSK HhhhHH 43.5 16.6 292.1 6.778914 1.4388e−11 1.00000 N 0.148922 0.056980 QxxxKT CcccHH 10.2 0.5 24.8 13.423552 3.5602e−11 1.00000 B 0.411290 0.021381 AxxxGA HhhhCC 26.9 8.1 515.8 6.675596 4.0624e−11 1.00000 N 0.052152 0.015659 WxxxYA CcccHH 5.0 0.0 5.3 25.164503 4.1132e−11 1.00000 B 0.943396 0.007387 NxxxDK CeeeEE 29.8 9.8 140.6 6.628627 5.1332e−11 1.00000 N 0.211949 0.069648 FxxxLT HhhhHH 24.0 6.8 425.0 6.631623 6.0285e−11 1.00000 N 0.056471 0.016048 AxxxGL HhhhCC 28.1 8.8 473.3 6.596022 6.5719e−11 1.00000 N 0.059370 0.018507 NxxxGG CchhHC 9.3 0.5 16.8 13.308464 9.4341e−11 1.00000 B 0.553571 0.027028 RxxxTD HcccCC 22.6 4.5 69.1 8.886497 9.5799e−11 1.00000 B 0.327062 0.064487 KxxxCH HcccCC 10.6 0.7 19.9 12.354502 9.7646e−11 1.00000 B 0.532663 0.033601 SxxxGR CcccCH 12.7 1.0 40.8 11.522791 1.0549e−10 1.00000 B 0.311275 0.025718 SxxxCW CcecHH 5.7 0.0 11.5 27.570955 1.2129e−10 1.00000 B 0.495652 0.003675 RxxxAE HhhhHH 57.2 25.4 630.5 6.432535 1.2154e−10 1.00000 N 0.090722 0.040326 LxxxGV HhhhCC 23.0 6.6 445.9 6.430108 2.2726e−10 1.00000 N 0.051581 0.014805 YxxxNR EcccEE 19.8 5.4 85.3 6.438949 2.5510e−10 1.00000 N 0.232122 0.062882 PxxxGK CcccCH 20.8 3.6 194.8 9.202084 2.5628e−10 1.00000 B 0.106776 0.018331 QxxxYG CcccHH 13.3 1.4 40.0 10.338918 3.4539e−10 1.00000 B 0.332500 0.034432 MxxxKF HcccCE 7.5 0.2 14.3 15.600641 4.0462e−10 1.00000 B 0.524476 0.015462 PxxxAL CchhHC 12.4 1.2 28.2 10.320780 4.9428e−10 1.00000 B 0.439716 0.043459 QxxxCH HhhhHH 13.0 1.5 31.0 9.683104 6.3845e−10 1.00000 B 0.419355 0.047912 AxxxNF CcccCE 8.6 0.4 31.7 13.879215 8.1895e−10 1.00000 B 0.271293 0.011254 NxxxNR HhchHH 13.9 1.6 49.3 9.721101 1.0469e−09 1.00000 B 0.281947 0.033353 NxxxLM CcccCE 5.0 0.1 6.3 19.458847 1.0490e−09 1.00000 B 0.793651 0.010316 RxxxGL CeccEC 6.2 0.2 6.0 13.456025 1.0888e−09 1.00000 B 1.033333 0.032074 NxxxTT CcchHH 15.8 2.3 52.5 9.154042 1.1764e−09 1.00000 B 0.300952 0.043434 KxxxQK EeccCC 8.2 0.5 9.5 10.982772 1.2202e−09 1.00000 B 0.863158 0.054473 KxxxGK HhhhCC 30.7 11.1 167.2 6.107252 1.3267e−09 1.00000 N 0.183612 0.066190 RxxxGL HhhcCC 21.0 6.1 160.0 6.156651 1.3396e−09 1.00000 N 0.131250 0.038087 ExxxAQ HhhhHH 43.6 18.2 430.8 6.069188 1.3445e−09 1.00000 N 0.101207 0.042332 RxxxGK HhhhCC 20.0 5.8 92.2 6.130584 1.6557e−09 1.00000 N 0.216920 0.062441 ExxxSR HhhhHH 34.5 13.2 256.4 6.044594 1.7844e−09 1.00000 N 0.134555 0.051287 MxxxRN HhhhCC 15.6 2.2 66.5 9.152082 1.8995e−09 1.00000 B 0.234586 0.033281 GxxxAH ChhhHH 11.0 1.0 33.0 10.168580 2.0150e−09 1.00000 B 0.333333 0.030234 HxxxGK CcccCH 9.0 0.5 49.3 11.829852 2.3778e−09 1.00000 B 0.182556 0.010535 NxxxSR HhhcCH 11.2 1.1 22.1 9.635067 2.6454e−09 1.00000 B 0.506787 0.051948 AxxxQK HhhhCE 18.1 3.5 52.2 8.157327 2.7384e−09 1.00000 B 0.346743 0.066142 QxxxGI HhhhCC 19.5 5.6 117.8 5.976186 4.1929e−09 1.00000 N 0.165535 0.047922 CxxxIG CcccCH 4.8 0.0 12.4 27.010872 4.6438e−09 1.00000 B 0.387097 0.002520 ExxxSK EcccCE 14.4 2.0 50.5 8.850457 5.1816e−09 1.00000 B 0.285149 0.040279 SxxxSL HhhhHC 17.8 3.1 114.3 8.385299 5.7237e−09 1.00000 B 0.155731 0.027490 GxxxKT CcccHH 18.5 3.4 134.6 8.307329 5.8961e−09 1.00000 B 0.137444 0.025205 RxxxQR HhhhHH 33.7 13.2 228.4 5.794345 7.8947e−09 1.00000 N 0.147548 0.057959 KxxxPG HhhcCC 28.5 10.4 157.6 5.811554 7.9723e−09 1.00000 N 0.180838 0.065945 AxxxCH CchhHH 6.0 0.1 5.0 14.128524 8.7129e−09 1.00000 B 1.200000 0.024436 RxxxGG HhhhCC 20.3 4.5 85.3 7.694509 9.8975e−09 1.00000 B 0.237984 0.052377 AxxxRH HhhhHH 29.4 10.9 245.6 5.749860 1.1049e−08 1.00000 N 0.119707 0.044253 CxxxIG CcccCC 9.5 0.7 40.6 10.749424 1.1320e−08 1.00000 B 0.233990 0.016851

TABLE 22 In Expected P-Value P-Value Observed Null Sequence Structure Epitopes in Epi In PDB Z-Score Upper Lower Distribution Ratio Probability GxxKxT CccHhH 83.1 9.8 353.1 23.760777 1.9863e−123 1.00000 N 0.235344 0.027728 TxxGxT CccChH 46.6 5.5 140.5 17.925581 1.8308e−70 1.00000 N 0.331673 0.038978 VxxKxG EccCcC 41.9 6.3 138.2 14.475018 1.6458e−46 1.00000 N 0.303184 0.045794 SxxVxK CeeEeE 65.3 16.6 303.8 12.309323 1.9144e−34 1.00000 N 0.214944 0.054555 QxxGxG CccChH 34.0 2.7 61.5 19.639877 3.0967e−30 1.00000 B 0.552846 0.043273 DxxGxG CccCcC 95.4 33.3 1003.2 10.953878 8.3945e−28 1.00000 N 0.095096 0.033166 CxxGxT CccCcC 36.2 3.3 126.6 18.275052 5.0452e−27 1.00000 B 0.285940 0.026253 RxxDxD HhhCcC 36.6 7.6 188.0 10.735002 2.5428e−26 1.00000 N 0.194681 0.040444 DxxGxT CccChH 25.3 1.6 63.1 19.072943 7.2871e−24 1.00000 B 0.400951 0.025131 PxxLxV CceEeE 32.3 6.5 409.9 10.154812 1.1669e−23 1.00000 N 0.078800 0.015954 TxxDxK EeeEeE 71.3 24.2 396.7 9.891898 6.4050e−23 1.00000 N 0.179733 0.060932 PxxNxG CeeCcC 15.5 0.3 24.8 26.829701 6.7903e−23 1.00000 B 0.625000 0.013072 DxxVxK CccCcH 23.6 1.5 120.5 18.328477 4.2756e−21 1.00000 B 0.195851 0.012242 LxxLxT HhhChH 14.7 0.4 21.1 23.070139 2.0329e−20 1.00000 B 0.696682 0.018575 FxxHxA CccHhH 11.6 0.2 19.0 27.924333 7.9156e−19 1.00000 B 0.610526 0.008899 RxxGxG CccChH 24.2 2.4 63.5 14.513003 1.7368e−18 1.00000 B 0.381102 0.037058 LxxNxM CchHhH 18.1 1.0 44.6 17.173637 1.8356e−18 1.00000 B 0.405830 0.022712 SxxGxT CccChH 30.5 4.0 129.8 13.540361 2.3842e−18 1.00000 B 0.234977 0.030525 NxxKxT CccHhH 23.8 2.3 62.4 14.345065 6.0409e−18 1.00000 B 0.381410 0.037298 SxxKxD HceEeE 57.0 19.8 313.1 8.642784 7.5321e−18 1.00000 N 0.182050 0.063201 YxxGxT HhcCcC 22.1 2.2 65.5 13.586630 1.4379e−16 1.00000 B 0.337405 0.033843 CxxGxG CccCcH 10.3 0.1 51.3 27.308055 1.8238e−16 1.00000 B 0.200780 0.002706 DxxGxP HhhCcC 33.8 9.3 183.0 8.241246 3.4292e−16 1.00000 N 0.184699 0.050855 LxxKxY HhhCcC 22.3 2.4 89.2 13.024128 1.5264e−15 1.00000 B 0.250000 0.026898 GxxKxS CccHhH 24.1 2.9 119.6 12.606859 1.6128e−15 1.00000 B 0.201505 0.024235 ExxGxS HhhCcC 35.4 10.4 185.6 7.959755 3.0861e−15 1.00000 N 0.190733 0.056187 KxxFxV HhcCcH 11.6 0.4 15.8 17.893079 3.6601e−15 1.00000 B 0.734177 0.025436 LxxAxK CccCcH 14.8 0.8 60.2 15.943519 9.6061e−15 1.00000 B 0.245847 0.013008 RxxMxS HhhEcC 16.7 1.3 42.2 13.801893 1.5849e−14 1.00000 B 0.395735 0.030483 MxxFxF HccCcE 7.5 0.1 12.0 30.033887 3.6712e−14 1.00000 B 0.625000 0.005138 MxxCxL EecCcC 7.0 0.1 10.0 26.697096 7.8298e−14 1.00000 B 0.700000 0.006788 YxxNxQ CccCcC 22.9 3.2 83.7 11.126181 1.4659e−13 1.00000 B 0.273596 0.038784 KxxGxD HhcCcC 46.7 17.0 284.7 7.415308 1.5458e−13 1.00000 N 0.164032 0.059814 AxxGxP HhcCcC 32.9 9.9 247.6 7.451189 1.5600e−13 1.00000 N 0.132876 0.040039 KxxGxN HhcCcC 33.4 10.3 186.4 7.375182 2.6922e−13 1.00000 N 0.179185 0.055503 SxxGxS CccChH 26.0 4.6 127.5 10.143807 8.1010e−13 1.00000 B 0.203922 0.036176 NxxCxN EecCcC 14.5 1.1 43.0 12.726677 1.5589e−12 1.00000 B 0.337209 0.026349 AxxKxT CccHhH 14.5 1.2 45.7 12.548421 2.4406e−12 1.00000 B 0.317287 0.025375 GxxGxC CccCcH 13.3 0.9 44.9 12.905411 3.8622e−12 1.00000 B 0.296214 0.020874 SxxAxW CceChH 5.2 0.0 5.0 29.896993 5.3267e−12 1.00000 B 1.040000 0.005563 KxxGxP HhhCcC 39.7 14.3 276.0 6.907485 6.3677e−12 1.00000 N 0.143841 0.051742 RxxGxA HhhCcC 21.2 5.4 114.5 6.985745 6.6680e−12 1.00000 N 0.185153 0.046994 RxxDxS EccCcC 20.5 5.1 138.7 6.971130 7.6462e−12 1.00000 N 0.147801 0.036621 ExxPxD HhcCcC 20.1 5.1 88.6 6.882766 1.4270e−11 1.00000 N 0.226862 0.057140 RxxGxP HhhCcC 35.0 12.1 274.9 6.707417 2.6783e−11 1.00000 N 0.127319 0.044184 NxxGxS CecCeC 18.6 2.8 49.7 9.784163 3.5481e−11 1.00000 B 0.374245 0.055768 ExxGxS HhcCcC 24.9 7.3 129.6 6.682720 4.2194e−11 1.00000 N 0.192130 0.056545 SxxWxS CccCcC 23.6 6.7 200.2 6.644325 5.6746e−11 1.00000 N 0.117882 0.033448 RxxGxN HhcCcC 27.5 8.6 166.0 6.600575 6.5622e−11 1.00000 N 0.165663 0.051959 SxxIxR CccCcH 9.7 0.4 26.0 14.293879 6.8602e−11 1.00000 B 0.373077 0.016455 GxxFxI EccEeE 8.2 0.3 14.4 14.787675 8.3777e−11 1.00000 B 0.569444 0.020271 NxxVxK CeeEeE 31.3 10.6 203.1 6.545306 8.4370e−11 1.00000 N 0.154111 0.052072 TxxLxK CccCcH 12.8 1.1 41.4 11.514712 9.3815e−11 1.00000 B 0.309179 0.025747 ExxGxP HhcCcC 32.8 11.5 226.1 6.450292 1.4987e−10 1.00000 N 0.145069 0.050838 MxxSxN HhhHcC 14.4 1.5 54.6 10.544362 1.5677e−10 1.00000 B 0.263736 0.028063 CxxNxC EccCcC 7.6 0.2 27.4 17.711018 1.6978e−10 1.00000 B 0.277372 0.006453 KxxGxN HhhCcC 32.1 11.2 196.9 6.425281 1.7880e−10 1.00000 N 0.163027 0.056929 SxxIxR CccChH 7.5 0.2 22.9 16.857018 2.8617e−10 1.00000 B 0.327511 0.008281 ExxLxY HhhHhC 17.0 2.5 69.1 9.239619 4.0465e−10 1.00000 B 0.246020 0.036788 GxxKxA CccHhH 21.1 3.9 165.6 8.815648 4.6376e−10 1.00000 B 0.127415 0.023544 RxxTxK HhcCcC 14.5 1.9 33.2 9.273239 9.5076e−10 1.00000 B 0.436747 0.058635 SxxTxC HhhCcE 5.3 0.0 4.0 26.740684 9.5757e−10 1.00000 B 1.325000 0.005563 RxxGxV HhhCcC 19.6 3.6 103.7 8.613509 1.4059e−09 1.00000 B 0.189007 0.034542 ExxGxV HhhCcC 21.1 4.3 110.4 8.311882 1.4089e−09 1.00000 B 0.191123 0.038646 AxxGxA HhhCcC 20.9 6.1 152.0 6.130139 1.5782e−09 1.00000 N 0.137500 0.040030 TxxGxT EecCeE 29.0 10.2 184.0 6.076901 1.6537e−09 1.00000 N 0.157609 0.055253 QxxTxK CccCcH 7.5 0.2 21.1 14.590222 1.7420e−09 1.00000 B 0.355450 0.011843 PxxSxK CccCcH 11.0 0.9 71.6 10.601684 2.0925e−09 1.00000 B 0.153631 0.012799 NxxPxR HhcHhH 13.9 1.8 59.3 9.320763 2.9671e−09 1.00000 B 0.234401 0.029523 DxxTxT EccCcE 19.9 3.9 104.8 8.202127 3.2719e−09 1.00000 B 0.189885 0.037557 PxxGxS HhhCeC 7.4 0.4 8.5 11.674578 3.5192e−09 1.00000 B 0.870588 0.044539 ExxGxL HhcCcC 20.8 4.3 112.8 8.112994 3.5599e−09 1.00000 B 0.184397 0.038122 AxxGxS HhhCcC 26.8 9.2 190.0 5.946894 3.7813e−09 1.00000 N 0.141053 0.048433 QxxCxS CccCeC 5.1 0.1 38.9 20.782682 3.9101e−09 1.00000 B 0.131105 0.001515 LxxSxK CccCcH 9.0 0.6 47.6 11.386026 4.1886e−09 1.00000 B 0.189076 0.011690 FxxAxN CchHhH 7.8 0.3 17.0 12.974151 4.3718e−09 1.00000 B 0.458824 0.019855 RxxGxE HhcCcC 30.2 11.2 186.3 5.834341 6.7156e−09 1.00000 N 0.162104 0.060330 AxxGxP HhhCcC 32.6 12.5 323.5 5.818734 6.9638e−09 1.00000 N 0.100773 0.038516 NxxDxD HhhCcC 14.0 2.0 57.2 8.641401 7.8927e−09 1.00000 B 0.244755 0.034942 RxxGxP HhcCcC 27.1 9.6 187.1 5.799118 8.8328e−09 1.00000 N 0.144842 0.051307 CxxGxM HhcCcH 8.0 0.4 26.4 11.413436 8.9920e−09 1.00000 B 0.303030 0.016879 LxxGxR HhcCcC 19.7 5.8 175.5 5.837346 9.1774e−09 1.00000 N 0.112251 0.033250 DxxExG EeeEcC 15.2 2.5 65.7 8.298279 1.2842e−08 1.00000 B 0.231355 0.037315 QxxSxW CccChH 6.1 0.2 25.7 14.525392 1.3369e−08 1.00000 B 0.237354 0.006532 IxxGxL HhhCcC 16.6 2.8 119.7 8.281164 1.3631e−08 1.00000 B 0.138680 0.023654 FxxMxR ChhHhH 9.7 0.8 22.6 10.065010 1.3976e−08 1.00000 B 0.429204 0.035808 LxxAxK EccCcH 7.0 0.3 14.5 11.645568 1.4353e−08 1.00000 B 0.482759 0.023123 LxxPxY CccCcC 20.5 6.3 212.2 5.742644 1.5087e−08 1.00000 N 0.096607 0.029693 ExxGxW CccCcE 9.0 0.7 32.0 10.221785 1.5374e−08 1.00000 B 0.281250 0.021165 NxxCxS CceEeC 5.5 0.1 5.5 14.257524 1.6946e−08 1.00000 B 1.000000 0.026344 GxxPxW CceCcC 6.0 0.3 7.0 11.416331 1.8807e−08 1.00000 B 0.857143 0.037489 RxxGxS HhcCcC 22.0 7.2 126.2 5.687773 1.9453e−08 1.00000 N 0.174326 0.056971 AxxGxT HhcCcC 20.6 6.5 145.6 5.653943 2.4711e−08 1.00000 N 0.141484 0.044679 DxxExL EhhHhH 13.6 1.9 70.0 8.562336 2.4756e−08 1.00000 B 0.194286 0.027355 ExxGxE HhhCcC 33.2 13.4 223.9 5.576582 2.7286e−08 1.00000 N 0.148280 0.059866 KxxHxY HhhCcC 7.0 0.4 11.3 10.460323 3.2212e−08 1.00000 B 0.619469 0.036433 PxxSxE CccChH 34.3 14.1 270.2 5.539452 3.2852e−08 1.00000 N 0.126943 0.052072 GxxTxY CccEeE 18.5 5.6 135.9 5.610971 3.4396e−08 1.00000 N 0.136130 0.040853 ExxGxR HhcCcC 18.1 5.4 95.5 5.613533 3.4784e−08 1.00000 N 0.189529 0.056691

TABLE 23 In Expected in P-Value P-Value Observed Null Sequence Structure Epitopes Epi In PDB Z-Score Upper Lower Distribution Ratio Probability TxxGKT CccCHH 42.4 2.6 117.2 24.985498 4.7047e−39 1.00000 B 0.361775 0.022146 SxxVDK CeeEEE 59.1 13.1 253.5 13.080308 1.3690e−38 1.00000 N 0.233136 0.051524 DxxGKT CccCHH 24.3 0.5 45.9 35.121431 5.7625e−36 1.00000 B 0.529412 0.010137 TxxDKK EeeEEE 69.9 18.8 364.0 12.105623 2.0737e−33 1.00000 N 0.192033 0.051630 GxxKTT CccHHH 37.1 3.0 141.8 19.967429 1.5635e−29 1.00000 B 0.261636 0.021032 YxxNFQ CccCCC 18.6 0.4 22.6 30.533644 3.4603e−29 1.00000 B 0.823009 0.016043 GxxKST CccHHH 30.9 2.1 110.3 19.885548 1.1670e−26 1.00000 B 0.280145 0.019346 QxxGLG CccCHH 16.0 0.4 16.7 24.595142 1.4620e−25 1.00000 B 0.958084 0.024661 DxxVGK CccCCH 20.6 0.6 102.6 24.935978 2.1888e−24 1.00000 B 0.200780 0.006281 LxxAGK CccCCH 14.8 0.2 46.4 35.352560 4.6640e−24 1.00000 B 0.318966 0.003704 SxxKVD HceEEE 56.5 16.4 313.0 10.172335 4.8080e−24 1.00000 N 0.180511 0.052395 SxxIGR CccCCH 9.7 0.0 14.7 71.755345 7.9503e−24 1.00000 B 0.659864 0.001240 SxxGKS CccCHH 25.0 1.5 91.5 19.260012 1.8449e−23 1.00000 B 0.273224 0.016527 SxxGNT CccCHH 12.5 0.1 11.0 31.354824 3.0442e−22 1.00000 B 1.136364 0.011065 LxxNVM CchHHH 18.1 0.7 30.9 20.921107 3.8340e−22 1.00000 B 0.585761 0.022891 RxxMDS HhhECC 16.7 0.4 42.2 24.919014 6.1180e−22 1.00000 B 0.395735 0.010205 CxxNIC EccCCC 7.0 0.0 12.0 90.555035 5.9489e−21 1.00000 B 0.583333 0.000497 NxxKTT CccHHH 15.8 0.5 24.1 20.868377 5.3869e−20 1.00000 B 0.655602 0.022683 PxxNIG CeeCCC 14.3 0.1 10.3 29.833145 6.0708e−20 1.00000 B 1.388350 0.011440 DxxGDG CccCCC 32.8 7.6 245.6 9.251579 6.0747e−20 1.00000 N 0.133550 0.031090 VxxKNG EccCCC 26.6 2.8 57.3 14.434463 1.7747e−19 1.00000 B 0.464223 0.049723 CxxGIG CccCCC 6.3 0.0 11.9 112.413301 2.0360e−19 1.00000 B 0.529412 0.000264 YxxGRT HhcCCC 18.3 1.0 35.4 17.340206 5.1270e−19 1.00000 B 0.516949 0.028879 SxxIGR CccCHH 7.3 0.0 20.2 61.430311 4.6706e−18 1.00000 B 0.361386 0.000697 NxxVDK CeeEEE 29.8 7.1 135.8 8.714799 7.8056e−18 1.00000 N 0.219440 0.052559 SxxVGR CccCHH 8.3 0.0 20.1 43.587327 9.6557e−18 1.00000 B 0.412935 0.001792 NxxVDN CeeECC 1.0 0.0 1.0 5.018033 1.0678e−16 1.00000 B 1.000000 0.038196 QxxFHI HhhHCC 1.6 0.0 1.0 5.358042 1.0729e−16 1.00000 B 1.600000 0.033660 YxxIHA EecCCC 1.5 0.0 1.0 6.463791 1.0843e−16 1.00000 B 1.500000 0.023375 DxxRFV CccCCE 1.0 0.0 1.0 6.799182 1.0867e−16 1.00000 B 1.000000 0.021173 TxxVFE CccEEC 1.0 0.0 1.0 9.900521 1.0990e−16 1.00000 B 1.000000 0.010099 GxxDNG CceEEE 1.0 0.0 1.0 10.153886 1.0996e−16 1.00000 B 1.000000 0.009606 DxxGNG CccCCC 30.0 4.5 174.5 12.117828 3.3659e−16 1.00000 B 0.171920 0.025984 AxxVGK CccCCH 8.6 0.1 32.0 33.752156 1.0516e−15 1.00000 B 0.268750 0.002003 PxxSGK CccCCH 11.0 0.2 54.7 21.809359 1.3203e−15 1.00000 B 0.201097 0.004466 KxxFTV HhcCCH 11.1 0.4 14.1 17.687177 1.7765e−15 1.00000 B 0.787234 0.026782 RxxTFK HhcCCC 11.0 0.5 11.5 15.520720 2.5051e−15 1.00000 B 0.956522 0.041692 GxxKTS CccHHH 13.9 0.6 33.5 16.756306 2.7900e−15 1.00000 B 0.414925 0.019061 QxxGKT CccCHH 10.2 0.2 23.0 21.950729 3.1726e−15 1.00000 B 0.443478 0.009090 DxxTGK CccCCH 8.0 0.1 31.4 29.149732 8.1205e−15 1.00000 B 0.254777 0.002360 LxxSGK CccCCH 9.0 0.1 31.2 24.222034 1.0197e−14 1.00000 B 0.288462 0.004312 QxxGYG CccCHH 12.3 0.6 20.1 15.259162 4.3218e−14 1.00000 B 0.611940 0.030129 MxxCTL EecCCC 7.0 0.1 9.0 26.919571 4.4228e−14 1.00000 B 0.777778 0.007425 QxxSCW CccCHH 6.1 0.0 20.2 40.736633 6.6470e−14 1.00000 B 0.301980 0.001103 MxxFKF HccCCE 7.5 0.1 10.7 26.539741 1.4215e−13 1.00000 B 0.700935 0.007362 GxxKSA CccHHH 14.5 0.9 56.2 14.356408 1.4566e−13 1.00000 B 0.258007 0.016205 LxxKDY HhhCCC 12.4 0.8 17.5 13.258420 4.4705e−13 1.00000 B 0.708571 0.045827 RxxGIG CccCHH 10.2 0.4 15.1 15.563661 4.7518e−13 1.00000 B 0.675497 0.026947 SxxACW CceCHH 5.2 0.0 4.0 67.545729 5.8875e−13 1.00000 B 1.300000 0.000876 GxxIMS CccHHH 5.0 0.0 5.8 38.483793 9.0813e−13 1.00000 B 0.862069 0.002899 CxxGVG CccCCH 5.8 0.0 18.8 42.983619 1.8140e−12 1.00000 B 0.308511 0.000963 KxxACK EeeCCC 15.3 1.4 42.0 11.769566 3.0198e−12 1.00000 B 0.364286 0.034205 GxxGKT CccCHH 16.5 1.7 115.5 11.634197 7.0138e−12 1.00000 B 0.142857 0.014306 NxxSGK CccCCH 5.5 0.0 10.0 35.698627 9.1312e−12 1.00000 B 0.550000 0.002359 QxxTGK CccCCH 7.5 0.1 16.1 20.225448 1.5596e−11 1.00000 B 0.465839 0.008308 IxxYTP EccCCC 9.6 0.3 54.6 16.103991 2.2522e−11 1.00000 B 0.175824 0.006102 NxxPNR HhcHHH 13.9 1.2 47.4 11.480225 3.1658e−11 1.00000 B 0.293249 0.026318 MxxSRN HhhHCC 13.4 1.2 42.0 11.445113 4.7252e−11 1.00000 B 0.319048 0.027951 NxxCKN EecCCC 13.3 1.2 43.0 11.287293 6.3736e−11 1.00000 B 0.309302 0.027552 SxxAGN EccCCC 7.0 0.2 7.1 13.993809 6.7483e−11 1.00000 B 0.985915 0.034010 AxxKTT CccHHH 9.0 0.4 21.5 13.833100 7.3110e−11 1.00000 B 0.418605 0.018337 ExxVGK CccCCH 7.7 0.2 34.6 18.607804 9.4920e−11 1.00000 B 0.222543 0.004762 VxxGCI HhcCCH 4.0 0.0 6.5 40.995245 1.0625e−10 1.00000 B 0.615385 0.001460 CxxGIG CccCCH 4.5 0.0 12.4 45.567392 1.0818e−10 1.00000 B 0.362903 0.000784 RxxPFN EecCCC 7.5 0.1 6.0 16.214277 1.2341e−10 1.00000 B 1.250000 0.022313 SxxGKT CccCHH 14.0 1.4 83.3 10.619350 1.7092e−10 1.00000 B 0.168067 0.017123 KxxACH HccCCC 7.0 0.1 6.0 15.752097 1.7322e−10 1.00000 B 1.166667 0.023610 TxxGKS CccCHH 10.6 0.6 35.1 12.475499 2.4413e−10 1.00000 B 0.301994 0.018470 LxxICR CccCCH 4.0 0.0 7.8 37.197058 2.9087e−10 1.00000 B 0.512821 0.001476 SxxWPS CccCCC 19.8 5.3 162.2 6.396654 3.2879e−10 1.00000 N 0.122072 0.032719 RxxLPE HhhCCC 11.6 0.9 30.6 11.271642 3.4023e−10 1.00000 B 0.379085 0.030226 RxxGLG CccCHH 6.3 0.1 10.8 18.190253 4.2775e−10 1.00000 B 0.583333 0.010816 KxxSPQ HhcCCC 5.2 0.1 7.1 21.929565 5.3759e−10 1.00000 B 0.732394 0.007812 VxxGKT CccCHH 10.0 0.6 44.3 11.867670 5.9907e−10 1.00000 B 0.225734 0.014269 DxxGGG ChhHCC 9.8 0.6 19.9 11.917268 6.6472e−10 1.00000 B 0.492462 0.030812 PxxGKG CccCHH 11.0 0.9 38.6 10.839654 8.0255e−10 1.00000 B 0.284974 0.023067 GxxLGR CccHHH 7.0 0.2 10.9 13.800966 8.0725e−10 1.00000 B 0.642202 0.022484 LxxGMV CeeEEE 3.3 0.0 8.2 68.087959 9.9956e−10 1.00000 B 0.402439 0.000286 LxxAGK EccCCH 7.0 0.2 13.5 13.633148 1.6346e−09 1.00000 B 0.518519 0.018502 TxxGVH CceEEE 5.3 0.0 4.5 26.658583 1.9226e−09 1.00000 B 1.177778 0.006292 SxxSLS EccEEE 19.5 5.5 109.4 6.102942 1.9949e−09 1.00000 N 0.178245 0.050489 TxxIGE EecCCE 6.3 0.2 6.3 13.360594 2.1393e−09 1.00000 B 1.000000 0.034090 GxxGSC CccCCH 7.1 0.2 32.1 14.576219 2.1556e−09 1.00000 B 0.221184 0.006981 GxxKSS CccHHH 10.2 0.8 37.0 10.871965 2.5245e−09 1.00000 B 0.275676 0.020771 GxxKSC CccHHH 8.5 0.4 19.9 12.276595 2.8204e−09 1.00000 B 0.427136 0.022147 CxxGGW CccCHH 3.0 0.0 10.9 55.906034 2.9320e−09 1.00000 B 0.275229 0.000264 DxxDIG CccCHH 6.0 0.2 9.5 14.714780 2.9576e−09 1.00000 B 0.631579 0.016864 AxxGDS CccCCC 10.8 0.8 106.3 11.008754 3.4357e−09 1.00000 B 0.101599 0.007781 WxxGYA CccCHH 5.0 0.0 4.0 22.536110 3.7289e−09 1.00000 B 1.250000 0.007814 KxxRME CccCCC 7.4 0.3 17.5 13.498147 3.7508e−09 1.00000 B 0.422857 0.016148 QxxGIM CccCHH 4.8 0.0 7.0 25.824874 3.9991e−09 1.00000 B 0.685714 0.004889 KxxHPY HhhCCC 6.5 0.3 6.6 12.654223 5.5331e−09 1.00000 B 0.984848 0.038395 NxxCGS CceEEC 5.5 0.1 5.0 14.589457 6.3685e−09 1.00000 B 1.100000 0.022951 GxxHDI CccCCH 6.0 0.3 6.1 11.668890 6.4387e−09 1.00000 B 0.983607 0.041485 GxxKTF CccHHH 8.0 0.5 17.8 11.183882 6.8420e−09 1.00000 B 0.449438 0.026180 VxxLMV EeeEEE 3.0 0.0 4.0 42.629167 7.5384e−09 1.00000 B 0.750000 0.001236 LxxFMR EccCCC 5.0 0.1 11.0 17.765741 7.6538e−09 1.00000 B 0.454545 0.007029 KxxGLD HhcCCC 15.6 2.5 68.8 8.533480 8.1840e−09 1.00000 B 0.226744 0.035744 GxxGFT HhhCCH 12.9 1.7 33.5 8.805582 8.4299e−09 1.00000 B 0.385075 0.050848

TABLE 24 In Expected in P-Value P-Value Observed Null Sequence Structure Epitopes Epi In PDB Z-Score Upper Lower Distribution Ratio Probability GxGxxT CcChhH 95.5 16.6 530.8 19.647819 3.4828e−85 1.00000 N 0.179917 0.031337 VxCxxG EcCccC 40.5 1.7 79.3 30.256305 1.7042e−45 1.00000 B 0.510719 0.021207 ExIxxW CcChhH 22.8 0.2 24.5 51.610706 8.9399e−45 1.00000 B 0.930612 0.007893 SxKxxK CeEeeE 64.0 14.8 237.7 13.179769 3.3609e−39 1.00000 N 0.269247 0.062429 TxTxxT CcCchH 32.0 1.2 56.5 28.650551 7.1879e−39 1.00000 B 0.566372 0.020916 GxSxxE CcChhH 92.3 27.3 563.9 12.762018 4.6873e−37 1.00000 N 0.163682 0.048374 LxPxxR CcHhhH 39.9 7.4 228.2 12.087836 5.8061e−33 1.00000 N 0.174847 0.032646 GxPxxQ CcChhH 38.5 7.2 136.1 11.993530 1.9062e−32 1.00000 N 0.282880 0.052856 NxTxxE CcChhH 54.0 13.3 264.7 11.434346 7.0416e−30 1.00000 N 0.204005 0.050340 GxTxxQ CcChhH 51.1 12.8 261.6 10.949601 1.6032e−27 1.00000 N 0.195336 0.049082 RxIxxF EeEccC 32.0 3.0 66.9 16.977592 3.0617e−25 1.00000 B 0.478326 0.045546 GxGxxS CcChhH 41.3 4.9 257.3 16.498267 3.7587e−25 1.00000 B 0.160513 0.019237 PxWxxG CeEccC 14.5 0.2 18.7 32.157769 9.6205e−25 1.00000 B 0.775401 0.010689 SxAxxR ChHhhH 47.9 13.4 257.1 9.692430 6.3584e−22 1.00000 N 0.186309 0.052044 QxPxxL EeCceE 34.6 7.9 344.0 9.568532 3.0272e−21 1.00000 N 0.100581 0.023093 DxAxxT CcCchH 22.1 1.4 57.2 17.870923 3.8331e−21 1.00000 B 0.386364 0.024086 NxGxxT CcChhH 25.8 2.5 65.9 15.098624 1.3414e−19 1.00000 B 0.391502 0.037617 LxExxI CcHhhH 31.2 7.4 297.3 8.889427 1.6173e−18 1.00000 N 0.104945 0.024787 TxVxxK EeEeeE 70.3 26.3 562.7 8.776302 2.0407e−18 1.00000 N 0.124933 0.046795 LxExxR CcHhhH 29.6 6.8 193.1 8.870479 2.0553e−18 1.00000 N 0.153288 0.035373 DxGxxK CcCccH 25.6 2.6 108.4 14.333505 6.4194e−18 1.00000 B 0.236162 0.024277 LxPxxQ CcHhhH 26.4 5.8 169.7 8.748374 6.9214e−18 1.00000 N 0.155569 0.033949 ExSxxE CcChhH 46.7 14.6 297.5 8.631726 9.6940e−18 1.00000 N 0.156975 0.048973 YxSxxT HhCccC 20.3 1.6 51.4 14.976341 2.1046e−17 1.00000 B 0.394942 0.031285 GxSxxN CeChhH 21.5 2.0 57.9 14.186410 6.8792e−17 1.00000 B 0.371330 0.033905 SxTxxD HcEeeE 58.2 21.1 334.4 8.334126 1.0029e−16 1.00000 N 0.174043 0.063172 RxDxxY EeEecC 1.0 0.0 1.0 6.479049 1.0844e−16 1.00000 B 1.000000 0.023268 GxSxxT CcChhH 25.9 5.9 139.5 8.404110 1.2643e−16 1.00000 N 0.185663 0.042356 PxHxxL CcHhhC 12.9 0.5 18.3 18.181695 2.5192e−16 1.00000 B 0.704918 0.026188 DxAxxQ ChHhhH 30.4 7.9 151.2 8.256938 3.4079e−16 1.00000 N 0.201058 0.051986 TxCxxC CcHhhH 14.7 0.9 13.5 14.119043 5.4430e−16 1.00000 B 1.088889 0.063426 GxSxxA CcChhH 30.1 7.8 260.9 8.142754 8.5659e−16 1.00000 N 0.115370 0.029738 TxAxxE ChHhhH 42.1 13.3 254.5 8.093575 9.1094e−16 1.00000 N 0.165422 0.052386 CxAxxG CcCccH 11.6 0.3 44.1 22.129643 9.5347e−16 1.00000 B 0.263039 0.005986 GxDxxQ CcChhH 29.0 7.4 147.4 8.106973 1.1979e−15 1.00000 N 0.196744 0.050510 SxYxxE ChHhhH 23.4 2.9 60.5 12.397158 1.2306e−15 1.00000 B 0.386777 0.047559 CxNxxT CcCccC 21.3 2.3 79.4 12.866017 4.0656e−15 1.00000 B 0.268262 0.028403 TxAxxK ChHhhH 33.7 9.7 179.1 7.910811 4.7461e−15 1.00000 N 0.188163 0.054259 SxSxxA CcChhH 28.4 7.3 190.0 7.931919 4.8305e−15 1.00000 N 0.149474 0.038609 CxGxxY EeCccC 16.0 1.2 54.7 13.787800 2.6979e−14 1.00000 B 0.292505 0.021585 LxDxxR CcHhhH 24.5 6.0 159.0 7.656071 4.7140e−14 1.00000 N 0.154088 0.038000 GxTxxD CcChhH 47.3 16.9 366.4 7.557245 5.3153e−14 1.00000 N 0.129094 0.046209 LxSxxR CcHhhH 20.0 2.2 79.5 12.061536 5.7006e−14 1.00000 B 0.251572 0.028083 NxKxxK CeEeeE 32.2 9.6 154.0 7.535957 8.5785e−14 1.00000 N 0.209091 0.062307 GxGxxA CcChhH 24.7 6.2 337.1 7.548724 1.0269e−13 1.00000 N 0.073272 0.018245 SxVxxS CcCchH 21.3 2.6 98.9 11.741540 1.0710e−13 1.00000 B 0.215369 0.026329 LxExxK CcHhhH 24.2 6.0 184.2 7.523785 1.2703e−13 1.00000 N 0.131379 0.032735 TxTxxE CcChhH 30.8 9.0 191.4 7.468604 1.4651e−13 1.00000 N 0.160920 0.046846 SxGxxC EeCccC 15.5 1.0 147.6 14.198789 1.5326e−13 1.00000 B 0.105014 0.007073 GxSxxD CcChhH 52.0 19.9 441.1 7.347550 2.3629e−13 1.00000 N 0.117887 0.045205 GxSxxQ CcChhH 32.5 9.9 203.2 7.392465 2.4290e−13 1.00000 N 0.159941 0.048517 FxVxxN CcHhhH 9.0 0.2 14.7 17.947861 3.1447e−13 1.00000 B 0.612245 0.016469 DxAxxE ChHhhH 48.7 18.3 339.8 7.304968 3.3650e−13 1.00000 N 0.143320 0.053861 FxTxxR ChHhhH 13.6 1.1 20.2 12.530961 6.0951e−13 1.00000 B 0.673267 0.052338 SxExxR ChHhhH 62.2 26.5 481.7 7.130862 1.0256e−12 1.00000 N 0.129126 0.055033 SxAxxE ChHhhH 40.7 14.4 301.5 7.112073 1.5082e−12 1.00000 N 0.134992 0.047697 MxTxxF HcCccE 7.5 0.1 11.8 22.356778 2.0200e−12 1.00000 B 0.635593 0.009346 RxSxxE CeEhhH 9.0 0.3 8.9 15.363457 2.1971e−12 1.00000 B 1.011236 0.036336 TxAxxQ ChHhhH 35.1 11.8 204.9 6.994651 3.8335e−12 1.00000 N 0.171303 0.057525 NxTxxR HhChhH 13.9 1.1 47.4 12.497161 5.0108e−12 1.00000 B 0.293249 0.022727 NxSxxD CcChhH 25.1 7.0 145.6 6.979942 5.7351e−12 1.00000 N 0.172390 0.048331 GxNxxE CcChhH 35.9 12.3 268.7 6.879201 8.2900e−12 1.00000 N 0.133606 0.045839 LxAxxR CcHhhH 23.3 4.1 144.3 9.678385 1.6775e−11 1.00000 B 0.161469 0.028167 FxGxxA CcChhH 13.1 1.1 51.0 11.868621 2.5395e−11 1.00000 B 0.256863 0.020630 QxRxxG CcCchH 11.8 0.9 20.3 11.983867 2.9355e−11 1.00000 B 0.581281 0.042817 SxGxxR CcCchH 13.2 1.0 69.8 12.021912 2.9539e−11 1.00000 B 0.189112 0.014882 ExDxxG HhCccC 20.8 5.4 144.5 6.752501 3.2182e−11 1.00000 N 0.143945 0.037384 AxGxxT CcChhH 14.7 1.4 71.0 11.378940 3.7774e−11 1.00000 B 0.207042 0.019643 DxAxxR ChHhhH 33.9 11.7 212.5 6.651301 3.9842e−11 1.00000 N 0.159529 0.055269 GxDxxA CcChhH 41.7 16.0 346.5 6.586367 5.2939e−11 1.00000 N 0.120346 0.046127 GxTxxE CcChhH 54.9 23.8 506.5 6.546520 5.9175e−11 1.00000 N 0.108391 0.046894 TxSxxE CcChhH 26.4 8.1 188.8 6.578130 7.8469e−11 1.00000 N 0.139831 0.042863 PxTxxQ CcChhH 21.7 5.9 173.7 6.591601 8.7031e−11 1.00000 N 0.124928 0.034126 TxDxxR CcHhhH 16.8 2.3 45.8 9.817220 9.5154e−11 1.00000 B 0.366812 0.050164 GxCxxC CcCccH 7.4 0.2 31.8 18.650457 9.8742e−11 1.00000 B 0.232704 0.004772 SxAxxA ChHhhH 31.9 10.8 324.7 6.517178 9.9192e−11 1.00000 N 0.098245 0.033327 AxGxxK CcCccH 15.1 1.7 77.9 10.453088 1.1289e−10 1.00000 B 0.193838 0.021614 QxRxxE CcChhH 21.8 4.2 68.2 8.849948 1.4429e−10 1.00000 B 0.319648 0.061734 GxDxxE CcChhH 36.8 13.7 254.3 6.426476 1.6131e−10 1.00000 N 0.144711 0.053792 NxAxxK ChHhhH 23.7 7.1 137.1 6.437742 2.1271e−10 1.00000 N 0.172867 0.051429 DxAxxD ChHhhH 28.7 9.5 168.1 6.409489 2.1528e−10 1.00000 N 0.170732 0.056547 TxAxxR ChHhhH 26.0 8.1 178.9 6.402991 2.4282e−10 1.00000 N 0.145333 0.045534 NxGxxK CcCccH 10.0 0.6 25.9 11.827359 3.0863e−10 1.00000 B 0.386100 0.024785 DxAxxA ChHhhH 40.7 16.0 424.8 6.306170 3.2326e−10 1.00000 N 0.095810 0.037604 NxGxxS CcChhH 15.0 1.9 51.5 9.590943 4.1423e−10 1.00000 B 0.291262 0.037466 GxGxxI EcCeeE 12.5 1.1 47.7 10.879784 4.3984e−10 1.00000 B 0.262055 0.023487 NxGxxV ChHhhH 10.2 0.6 56.2 12.284253 4.6883e−10 1.00000 B 0.181495 0.010952 KxSxxE CcChhH 34.8 13.0 249.7 6.189193 7.3797e−10 1.00000 N 0.139367 0.052226 CxGxxC EcCccC 7.5 0.2 22.1 15.600743 7.6434e−10 1.00000 B 0.339367 0.009952 SxTxxE CcChhH 26.3 8.6 179.1 6.210132 7.9457e−10 1.00000 N 0.146845 0.047823 TxGxxT EeCceE 20.6 5.9 114.1 6.222362 9.2284e−10 1.00000 N 0.180543 0.051636 SxAxxQ ChHhhH 32.9 12.2 229.7 6.116524 1.1926e−09 1.00000 N 0.143230 0.052898 NxAxxR ChHhhH 18.8 3.4 71.1 8.575669 1.4009e−09 1.00000 B 0.264416 0.047686 RxRxxN EeCccC 11.5 1.1 29.6 10.340734 1.5733e−09 1.00000 B 0.388514 0.035728 LxDxxK CcHhhH 18.8 3.3 105.3 8.623619 1.8769e−09 1.00000 B 0.178538 0.031578 GxNxxQ CcChhH 20.6 4.1 96.7 8.325608 1.9155e−09 1.00000 B 0.213030 0.042410 HxCxxH CcCchH 9.8 0.8 14.2 10.365943 2.3489e−09 1.00000 B 0.690141 0.056264 FxHxxH EcHhhH 8.0 0.5 10.3 10.594488 2.7755e−09 1.00000 B 0.776699 0.050930 NxFxxA HcCchH 7.3 0.3 12.0 12.967742 2.9756e−09 1.00000 B 0.608333 0.024910

TABLE 25 In Expected in P-Value P-Value Observed Null Sequence Structure Epitopes Epi In PDB Z-Score Upper Lower Distribution Ratio Probability SxKxDK CeEeEE 56.6 10.6 226.5 14.510498 5.1077e−47 1.00000 N 0.249890 0.046621 TxTxKT CcCcHH 27.3 0.4 35.1 41.402645 3.3263e−45 1.00000 B 0.777778 0.012151 TxVxKK EeEeEE 68.9 17.0 371.5 12.858963 1.8898e−37 1.00000 N 0.185464 0.045880 DxAxKT CcCcHH 21.3 0.3 36.1 42.228224 1.7463e−36 1.00000 B 0.590028 0.006931 VxCxNG EcCcCC 27.6 1.3 56.3 22.965619 2.7459e−29 1.00000 B 0.490231 0.023790 SxTxVD HcEeEE 57.7 15.5 332.4 10.970812 1.1028e−27 1.00000 N 0.173586 0.046666 DxGxGK CcCcCH 23.6 0.8 90.6 25.557645 2.7107e−27 1.00000 B 0.260486 0.008861 GxGxTT CcChHH 38.1 3.9 150.8 17.412946 2.6727e−26 1.00000 B 0.252653 0.026192 GxGxST CcChHH 33.8 3.1 132.3 17.712534 5.1241e−25 1.00000 B 0.255480 0.023279 SxGxGR CcCcHH 13.2 0.1 48.5 43.386267 6.4655e−25 1.00000 B 0.272165 0.001886 SxTxNT CcCcHH 12.5 0.1 11.0 29.834372 8.9716e−22 1.00000 B 1.136364 0.012207 NxKxDK CeEeEE 29.8 6.4 135.4 9.482096 8.5112e−21 1.00000 N 0.220089 0.047229 QxPxSL EeCcEE 27.9 5.8 253.4 9.267533 6.6594e−20 1.00000 N 0.110103 0.022941 YxSxRT HhCcCC 17.3 0.9 30.2 18.031141 3.4196e−19 1.00000 B 0.572848 0.028343 CxGxIC EcCcCC 7.0 0.0 12.0 65.805632 5.1452e−19 1.00000 B 0.583333 0.000941 SxVxKS CcCcHH 15.3 0.5 48.4 20.089608 3.7836e−18 1.00000 B 0.316116 0.011271 NxGxTT CcChHH 15.8 0.7 25.1 17.983191 4.6058e−18 1.00000 B 0.629482 0.028833 PxWxIG CeEcCC 12.3 0.1 9.3 27.308812 1.0008e−17 1.00000 B 1.322581 0.012317 PxHxAL CcHhHC 11.0 0.3 13.1 20.593235 3.3394e−17 1.00000 B 0.839695 0.021144 HxAxVA EeEeCC 3.0 0.0 1.0 4.880275 1.0655e−16 1.00000 B 3.000000 0.040295 RxTxDD EeEhHH 1.5 0.0 1.0 5.879538 1.0790e−16 1.00000 B 1.500000 0.028114 DxSxNT CcEhHH 1.0 0.0 1.0 6.087175 1.0810e−16 1.00000 B 1.000000 0.026279 LxAxVK ChHhHH 1.0 0.0 1.0 6.162276 1.0817e−16 1.00000 B 1.000000 0.025658 NxFxDS HhHcCC 1.0 0.0 1.0 6.660356 1.0857e−16 1.00000 B 1.000000 0.022046 YxIxTG EcCcCC 1.0 0.0 1.0 7.772472 1.0921e−16 1.00000 B 1.000000 0.016284 MxYxKI CcEeCC 1.5 0.0 1.0 8.569222 1.0953e−16 1.00000 B 1.500000 0.013435 GxGxTS CcChHH 13.9 0.6 32.9 18.152055 3.8821e−16 1.00000 B 0.422492 0.016720 PxGxGK CcCcCH 19.0 1.4 130.3 14.923143 4.2284e−16 1.00000 B 0.145817 0.010785 KxVxCK EeEcCC 17.6 1.4 47.7 14.183369 3.3780e−15 1.00000 B 0.368973 0.028318 AxGxGK CcCcCH 13.3 0.5 57.6 17.711953 4.1489e−15 1.00000 B 0.230903 0.009115 CxAxIG CcCcCC 8.5 0.1 15.5 25.381903 2.8396e−14 1.00000 B 0.548387 0.007100 LxNxGK CcCcCH 8.3 0.1 15.0 24.590088 4.0805e−14 1.00000 B 0.553333 0.007448 SxGxGC EeCcCC 15.3 1.0 130.5 14.714935 5.5466e−14 1.00000 B 0.117241 0.007334 NxGxGK CcCcCH 9.0 0.2 15.0 19.702967 6.8088e−14 1.00000 B 0.600000 0.013474 SxGxGR CcCcCH 8.5 0.1 23.1 24.809324 8.9712e−14 1.00000 B 0.367965 0.004970 LxNxCR CcCcCH 5.5 0.0 10.6 51.644952 2.5159e−13 1.00000 B 0.518868 0.001067 QxGxCW CcCcHH 7.9 0.1 20.2 25.311731 4.5137e−13 1.00000 B 0.391089 0.004729 CxAxVG CcCcCH 6.8 0.0 17.8 31.472647 1.0357e−12 1.00000 B 0.382022 0.002594 LxGxGK CcCcCH 12.9 0.7 55.2 14.339566 1.0848e−12 1.00000 B 0.233696 0.013224 NxTxNR HhChHH 13.8 1.0 47.4 13.035204 2.7237e−12 1.00000 B 0.291139 0.020818 MxTxKF HcCcCE 7.5 0.1 11.8 20.657897 5.9295e−12 1.00000 B 0.635593 0.010909 QxSxKT CcCcHH 7.2 0.1 17.7 21.756070 6.1332e−12 1.00000 B 0.406780 0.006042 AxRxNF CcCcCE 7.3 0.1 18.3 21.494990 8.0400e−12 1.00000 B 0.398907 0.006148 QxGxGK CcCcCH 11.5 0.6 50.9 14.221165 8.7531e−12 1.00000 B 0.225933 0.011689 TxNxGE EeCcCE 7.5 0.2 7.5 15.735409 2.9385e−11 1.00000 B 1.000000 0.029400 IxNxTP EcCcCC 9.6 0.3 51.6 15.771712 3.0578e−11 1.00000 B 0.186047 0.006716 CxAxIG CcCcCH 4.8 0.0 9.7 49.375090 3.2308e−11 1.00000 B 0.494845 0.000971 TxCxVH CcEeEE 5.3 0.0 7.0 29.062670 3.3981e−11 1.00000 B 0.757143 0.004714 YxDxFQ CcCcCC 6.8 0.1 16.8 23.103835 3.7298e−11 1.00000 B 0.404762 0.005054 AxNxRV CcChHH 8.3 0.1 6.4 18.908717 4.2509e−11 1.00000 B 1.296875 0.017585 GxGxSA CcChHH 14.5 1.5 84.5 10.890707 1.2556e−10 1.00000 B 0.171598 0.017267 AxGxTT CcChHH 9.0 0.4 22.7 13.379300 1.3988e−10 1.00000 B 0.396476 0.018462 SxGxCW CcEcHH 5.7 0.0 11.5 27.137424 1.4181e−10 1.00000 B 0.495652 0.003792 RxRxFN EeCcCC 7.5 0.1 6.0 15.932390 1.5159e−10 1.00000 B 1.250000 0.023091 QxSxGA CcCcEC 5.2 0.1 5.0 21.291482 1.5452e−10 1.00000 B 1.040000 0.010909 MxLxTL EeCcCC 7.0 0.2 11.1 15.638597 1.6234e−10 1.00000 B 0.630631 0.017371 TxSxKT CcCcHH 10.5 0.6 48.6 12.982231 1.7709e−10 1.00000 B 0.216049 0.012137 DxHxIG CcCcHH 6.0 0.1 7.3 17.182429 2.0446e−10 1.00000 B 0.821918 0.016313 NxQxQF CcCcCE 10.1 0.6 29.2 11.908196 3.6689e−10 1.00000 B 0.345890 0.022079 LxVxMV CeEeEE 3.3 0.0 9.0 78.494593 4.4384e−10 1.00000 B 0.366667 0.000196 QxQxIM CcCcHH 4.8 0.0 5.0 31.368999 4.7125e−10 1.00000 B 0.960000 0.004659 RxVxYT EeCcCC 9.1 0.5 23.1 12.387539 5.4387e−10 1.00000 B 0.393939 0.021353 HxDxGK CcCcCH 8.0 0.3 38.9 13.707911 9.2865e−10 1.00000 B 0.205656 0.008142 GxGxGR CcChHH 8.0 0.4 11.6 11.785433 1.0014e−09 1.00000 B 0.689655 0.036945 WxHxYA CcCcHH 5.0 0.0 4.0 24.146704 2.1553e−09 1.00000 B 1.250000 0.006814 WxNxFT HhHcCC 5.9 0.1 9.1 18.284331 2.4343e−09 1.00000 B 0.648352 0.011176 FxExLT HhHhHH 14.2 1.8 105.3 9.392605 2.8537e−09 1.00000 B 0.134853 0.016894 NxFxVA HcCcHH 6.3 0.2 8.0 14.231463 3.2657e−09 1.00000 B 0.787500 0.023607 GxTxKT CcCcHH 8.0 0.4 32.0 12.304709 3.7481e−09 1.00000 B 0.250000 0.012108 GxGxSS CcChHH 10.7 0.9 51.2 10.727384 4.1924e−09 1.00000 B 0.208984 0.016726 VxWxRG EeEcCC 4.6 0.0 5.3 24.562668 5.3187e−09 1.00000 B 0.867925 0.006561 ExGxSK EcCcCE 12.8 1.5 47.4 9.353019 5.8809e−09 1.00000 B 0.270042 0.031772 SxGxGK CcCcCH 8.6 0.5 34.6 12.115751 6.1620e−09 1.00000 B 0.248555 0.013228 QxRxYG CcCcHH 6.8 0.2 9.1 13.511358 6.4034e−09 1.00000 B 0.747253 0.026595 TxPxVY EcCeEE 8.3 0.4 243.9 12.511059 7.2393e−09 1.00000 B 0.034030 0.001638 VxHxKT CcCcHH 6.5 0.2 27.7 15.523646 7.7837e−09 1.00000 B 0.234657 0.006044 YxFxLH CcEeEE 4.0 0.0 4.0 20.532673 7.8032e−09 1.00000 B 1.000000 0.009399 DxRxTG EeEeCC 13.2 1.7 50.0 8.897809 8.4666e−09 1.00000 B 0.264000 0.034462 GxVxKS CcCcHH 9.1 0.6 60.0 10.783366 1.1852e−08 1.00000 B 0.151667 0.010405 AxTxKS CcCcHH 4.0 0.0 5.5 21.215041 1.4941e−08 1.00000 B 0.727273 0.006391 GxCxSC CcCcCH 4.6 0.0 29.3 25.245739 1.5299e−08 1.00000 B 0.156997 0.001118 GxGxSI EcCeEE 5.5 0.1 7.2 15.694859 1.5981e−08 1.00000 B 0.763889 0.016598 KxYxME CcCcCC 8.4 0.5 19.0 10.767521 1.6629e−08 1.00000 B 0.442105 0.028822 ExCxLG EcCcCC 5.0 0.1 5.8 13.975310 1.9806e−08 1.00000 B 0.862069 0.021445 DxGxTT CcChHH 9.6 0.8 37.4 10.287614 1.9873e−08 1.00000 B 0.256684 0.020174 NxAxKN EeCcCC 13.3 1.9 44.0 8.403028 2.1730e−08 1.00000 B 0.302273 0.043597 SxVxKT EeEeEE 11.0 1.3 38.0 8.833970 2.7438e−08 1.00000 B 0.289474 0.033101 GxGxSC CcChHH 8.5 0.6 21.8 10.479758 2.9812e−08 1.00000 B 0.389908 0.026882 RxGxGR CcChHH 7.5 0.4 12.0 10.790353 3.2673e−08 1.00000 B 0.625000 0.037003 GxTxEK CeEeEE 13.1 2.0 43.0 8.118745 3.5492e−08 1.00000 B 0.304651 0.045807 GxSxET CcChHH 11.7 1.4 40.7 8.739976 4.0137e−08 1.00000 B 0.287469 0.035156 GxGxSN CcChHH 6.3 0.2 15.3 12.729469 4.2660e−08 1.00000 B 0.411765 0.015085 SxSxKS CcCcHH 7.7 0.4 27.8 11.446286 4.3518e−08 1.00000 B 0.276978 0.014804 LxPxEF CcChHH 7.0 0.4 10.5 10.018015 4.4979e−08 1.00000 B 0.666667 0.042563 IxGxSA HhCcHH 5.0 0.2 5.0 11.874412 4.7104e−08 1.00000 B 1.000000 0.034246 GxDxYR CcCcEC 14.6 2.5 56.5 7.900639 5.0007e−08 1.00000 B 0.258407 0.043651 QxRxLG CcCcHH 5.0 0.1 8.0 13.885421 5.0566e−08 1.00000 B 0.625000 0.015651 VxFxFP CcCcCC 8.6 0.7 16.0 9.682042 5.1444e−08 1.00000 B 0.537500 0.043541 NxFxGS CcEeEC 5.5 0.2 5.0 11.627430 5.7697e−08 1.00000 B 1.100000 0.035664

TABLE 26 In Expected in P-Value P-Value Observed Null Sequence Structure Epitopes Epi In PDB Z-Score Upper Lower Distribution Ratio Probability GxGKxT CcCHhH 78.2 4.7 290.1 34.047316 1.1506e−69 1.00000 B 0.269562 0.016316 SxKVxK CeEEeE 59.8 11.1 226.5 14.982640 4.7717e−50 1.00000 N 0.264018 0.049037 TxTGxT CcCChH 31.0 0.7 40.9 36.555165 1.3620e−46 1.00000 B 0.757946 0.017091 VxCKxG EcCCcC 37.2 1.7 58.6 27.646791 3.2831e−42 1.00000 B 0.634812 0.028979 DxAGxT CcCChH 21.3 0.2 35.9 45.944381 5.1346e−38 1.00000 B 0.593315 0.005903 TxVDxK EeEEeE 69.3 18.1 368.2 12.323075 1.5043e−34 1.00000 N 0.188213 0.049248 NxGKxT CcCHhH 23.8 0.7 46.8 27.221369 5.7232e−30 1.00000 B 0.508547 0.015591 GxGKxS CcCHhH 23.6 0.7 72.6 26.546387 2.5060e−28 1.00000 B 0.325069 0.010313 SxTKxD HcEEeE 56.0 15.5 313.0 10.555618 9.5006e−26 1.00000 N 0.178914 0.049499 FxGHxA CcCHhH 10.6 0.1 13.0 40.140334 2.0626e−21 1.00000 B 0.815385 0.005323 CxAGxG CcCCcH 10.3 0.1 39.0 42.746343 2.0803e−20 1.00000 B 0.264103 0.001474 AxGKxT CcCHhH 14.4 0.3 36.4 25.127009 3.3324e−20 1.00000 B 0.395604 0.008706 DxGVxK CcCCcH 15.1 0.4 50.9 23.714451 3.6388e−20 1.00000 B 0.296660 0.007620 NxKVxK CeEEeE 30.8 6.9 138.8 9.289826 4.7236e−20 1.00000 N 0.221902 0.050018 PxWNxG CeECcC 13.5 0.1 10.5 30.708828 4.8231e−20 1.00000 B 1.285714 0.011012 YxSGxT HhCCcC 18.3 0.9 32.0 18.088408 6.9501e−20 1.00000 B 0.571875 0.029635 CxNGxT CcCCcC 19.0 1.2 51.6 16.572407 2.1832e−18 1.00000 B 0.368217 0.022926 SxVGxS CcCChH 15.3 0.6 42.3 19.232519 8.8090e−18 1.00000 B 0.361702 0.014021 TxDDxQ EhHHhH 1.0 0.0 1.0 5.392626 1.0733e−16 1.00000 B 1.000000 0.033244 CxGNxC EcCCcC 7.5 0.0 17.1 48.331529 1.0735e−16 1.00000 B 0.438596 0.001401 AxKLxP EeCCcC 1.7 0.0 1.0 5.966017 1.0799e−16 1.00000 B 1.700000 0.027327 FxISxI HcCCcE 1.8 0.0 1.0 5.996760 1.0802e−16 1.00000 B 1.800000 0.027055 MxYIxI CcEEcC 1.5 0.0 1.0 7.242638 1.0895e−16 1.00000 B 1.500000 0.018707 YxKIxA EeCCcC 1.5 0.0 1.0 7.671739 1.0917e−16 1.00000 B 1.500000 0.016707 SxTGxT CcCChH 14.5 0.7 35.5 17.037291 7.8231e−16 1.00000 B 0.408451 0.018915 SxGVxR CcCChH 7.3 0.0 19.1 37.942945 3.5076e−15 1.00000 B 0.382199 0.001922 GxGKxA CcCHhH 15.5 0.8 83.3 16.034987 4.2733e−15 1.00000 B 0.186074 0.010132 MxLCxL EeCCcC 7.0 0.0 9.1 31.828768 4.5925e−15 1.00000 B 0.769231 0.005270 GxGFxI EcCEeE 8.2 0.1 10.9 24.137133 1.5684e−14 1.00000 B 0.752294 0.010406 PxGSxK CcCCcH 11.0 0.4 37.7 17.974037 4.3376e−14 1.00000 B 0.291777 0.009394 VxWGxG EeECcC 15.8 1.1 116.6 14.134376 1.1466e−13 1.00000 B 0.135506 0.009373 SxGIxR CcCChH 5.9 0.0 20.2 52.593321 1.5200e−13 1.00000 B 0.292079 0.000621 MxTFxF HcCCcE 7.5 0.1 10.7 26.233866 1.6674e−13 1.00000 B 0.700935 0.007532 LxNAxK CcCCcH 6.3 0.0 10.5 34.674409 2.0201e−13 1.00000 B 0.600000 0.003121 QxRGxG CcCChH 11.8 0.6 17.1 14.463365 3.4044e−13 1.00000 B 0.690058 0.036257 SxGIxR CcCCcH 7.5 0.1 16.7 25.614984 6.6714e−13 1.00000 B 0.449102 0.005044 NxACxN EeCCcC 14.3 1.1 43.0 12.984350 9.3387e−13 1.00000 B 0.332558 0.024775 NxTPxL CcCCcC 11.8 0.6 39.8 14.917012 1.9147e−12 1.00000 B 0.296482 0.014437 NxTPxR HhCHhH 13.9 1.0 46.4 12.909302 2.3592e−12 1.00000 B 0.299569 0.021942 DxDGxG CcCCcC 35.9 11.9 416.7 7.054973 2.4585e−12 1.00000 N 0.086153 0.028573 DxGTxK CcCCcH 8.0 0.2 31.0 18.449093 9.3255e−12 1.00000 B 0.258065 0.005829 SxGAxW CcEChH 5.2 0.0 5.0 26.461826 1.7914e−11 1.00000 B 1.040000 0.007090 SxYQxE ChHHhH 14.9 1.6 34.9 10.894015 1.9565e−11 1.00000 B 0.426934 0.044931 KxYRxE CcCCcC 11.8 0.8 21.3 12.330460 1.9943e−11 1.00000 B 0.553991 0.038696 QxKGxG CcCChH 10.0 0.6 14.0 12.292249 2.1041e−11 1.00000 B 0.714286 0.043579 GxSIxG CeEEeE 9.5 0.3 35.1 15.756244 2.2978e−11 1.00000 B 0.270655 0.009721 AxGVxK CcCCcH 7.6 0.1 32.6 20.714517 2.3926e−11 1.00000 B 0.233129 0.004005 QxGTxK CcCCcH 7.5 0.1 16.6 19.297999 3.0906e−11 1.00000 B 0.451807 0.008825 GxGIxS CcCHhH 9.9 0.4 25.9 14.435885 3.2374e−11 1.00000 B 0.382239 0.016875 FxVAxN CcHHhH 7.8 0.2 10.5 17.204917 3.4705e−11 1.00000 B 0.742857 0.018948 SxKPxY CcCCcC 12.3 1.0 23.8 11.403495 4.1050e−11 1.00000 B 0.516807 0.042941 SxSGxS CcCChH 7.7 0.2 22.4 18.639391 6.4291e−11 1.00000 B 0.343750 0.007350 CxAGxG CcCCcC 8.3 0.3 28.1 16.106786 8.0611e−11 1.00000 B 0.295374 0.008965 QxSGxT CcCChH 7.2 0.2 19.1 17.864972 9.7007e−11 1.00000 B 0.376963 0.008205 GxGKxF CcCHhH 9.0 0.4 20.6 12.995440 1.8542e−10 1.00000 B 0.436893 0.021509 LxGAxK CcCCcH 6.5 0.1 16.9 20.766526 1.8659e−10 1.00000 B 0.384615 0.005660 KxQSxQ HhCCcC 5.2 0.0 7.1 23.500158 2.7200e−10 1.00000 B 0.732394 0.006815 DxPExL EhHHhH 12.7 1.2 38.0 10.917952 2.7228e−10 1.00000 B 0.334211 0.030355 GxCGxC CcCCcH 7.4 0.2 31.3 17.167182 2.9306e−10 1.00000 B 0.236422 0.005687 VxHGxT CcCChH 6.5 0.1 27.3 20.643805 2.9544e−10 1.00000 B 0.238095 0.003537 GxGKxN CcCHhH 6.3 0.1 19.0 19.922337 3.2745e−10 1.00000 B 0.331579 0.005128 NxGRxV ChHHhH 7.3 0.2 22.1 16.537083 3.4130e−10 1.00000 B 0.330317 0.008444 FxTMxR ChHHhH 9.5 0.5 17.4 12.380879 3.5175e−10 1.00000 B 0.545977 0.031061 KxVAxK EeECcC 15.3 2.0 42.0 9.504713 4.1563e−10 1.00000 B 0.364286 0.048679 LxNIxR CcCCcH 4.0 0.0 7.8 34.838623 4.8974e−10 1.00000 B 0.512821 0.001682 DxRExG EeEEcC 14.2 1.7 48.0 9.784977 5.8536e−10 1.00000 B 0.295833 0.035279 DxQAxC HhHHhH 12.0 1.1 49.1 10.414659 8.3369e−10 1.00000 B 0.244399 0.022756 NxGSxK CcCCcH 4.0 0.0 4.6 28.935098 8.3475e−10 1.00000 B 0.869565 0.004132 RxVNxT EeCCcC 9.1 0.5 26.4 12.189591 8.6890e−10 1.00000 B 0.344697 0.019193 NxRGxS CeCCeC 15.2 2.1 44.0 9.190897 9.0030e−10 1.00000 B 0.345455 0.048322 RxQGxG CcCChH 7.7 0.3 8.6 12.844513 9.3322e−10 1.00000 B 0.895349 0.039740 QxQGxG CcCChH 7.0 0.3 9.8 13.041557 1.1860e−09 1.00000 B 0.714286 0.027924 DxGKxT CcCHhH 10.5 0.7 46.5 11.532441 1.2908e−09 1.00000 B 0.225806 0.015683 GxTGxT CcCChH 8.2 0.3 36.7 13.463242 1.3489e−09 1.00000 B 0.223433 0.009366 NxGKxS CcCHhH 8.0 0.4 16.1 12.288612 1.4453e−09 1.00000 B 0.496894 0.024397 IxGSxK CcCCcH 4.0 0.0 6.0 28.717832 1.5897e−09 1.00000 B 0.666667 0.003213 PxSLxV CcEEeE 19.5 3.5 165.5 8.628967 1.9034e−09 1.00000 B 0.117825 0.021201 SxVExT EeEEeE 12.4 1.4 30.8 9.647297 2.1655e−09 1.00000 B 0.402597 0.044428 GxGYxT CcCHhH 7.5 0.3 11.7 13.194752 2.3128e−09 1.00000 B 0.641026 0.026093 TxCGxH CcEEeE 5.3 0.0 4.0 23.792462 2.4238e−09 1.00000 B 1.325000 0.007017 RxRPxN EeCCcC 8.5 0.5 19.0 12.095644 3.2320e−09 1.00000 B 0.447368 0.023862 VxGYxT CcCHhH 6.0 0.2 6.1 12.352805 3.3436e−09 1.00000 B 0.983607 0.037190 RxTGxS EeCCcC 12.3 1.3 50.0 9.683731 3.9672e−09 1.00000 B 0.246000 0.026408 GxGKxC CcCHhH 8.5 0.5 23.7 12.085767 4.5202e−09 1.00000 B 0.358650 0.019074 KxKAxH HcCCcC 5.0 0.1 5.0 14.665940 6.0513e−09 1.00000 B 1.000000 0.022718 DxHDxG CcCChH 6.0 0.2 10.8 13.860542 7.7869e−09 1.00000 B 0.555556 0.016605 QxGSxW CcCChH 6.1 0.2 24.7 15.059254 8.6876e−09 1.00000 B 0.246964 0.006346 CxGGxM HhCCcH 8.0 0.4 26.4 11.415826 8.9656e−09 1.00000 B 0.303030 0.016873 NxFCxS CcEEeC 5.5 0.1 5.0 13.483966 1.3733e−08 1.00000 B 1.100000 0.026764 KxSQxK EeCCcC 6.0 0.0 4.0 18.700567 1.6355e−08 1.00000 B 1.500000 0.011309 TxNIxE EeCCcE 6.3 0.3 6.3 11.104803 1.7890e−08 1.00000 B 1.000000 0.048605 NxFTxA HcCChH 6.3 0.2 8.6 12.485050 1.8314e−08 1.00000 B 0.732558 0.028168 ExGGxW CcCCcE 6.5 0.2 13.3 13.527432 1.8754e−08 1.00000 B 0.488722 0.016480 TxAQxE ChHHhH 10.1 1.0 32.5 9.403815 2.1503e−08 1.00000 B 0.310769 0.029888 TxVFxN EeEEcC 5.4 0.1 11.2 16.298617 2.3107e−08 1.00000 B 0.482143 0.009509 RxDTxQ HhCCcC 5.5 0.1 5.2 13.252766 2.4042e−08 1.00000 B 1.057692 0.028755 DxEGxP HhHCcC 15.1 2.6 55.1 7.886866 2.6898e−08 1.00000 B 0.274047 0.047668 GxGFxL EcCEeE 4.3 0.0 5.9 20.203205 3.1103e−08 1.00000 B 0.728814 0.007577 FxYSxD CcCCcC 5.9 0.2 8.0 13.568243 3.5331e−08 1.00000 B 0.737500 0.022718

TABLE 27 In Expected in P-Value P-Value Observed Null Sequence Structure Epitopes Epi In PDB Z-Score Upper Lower Distribution Ratio Probability SxKVDK CeEEEE 55.6 9.0 226.6 15.848462 1.0626e−55 1.00000 N 0.245366 0.039728 TxVDKK EeEEEE 68.9 14.4 363.1 14.631509 6.3100e−48 1.00000 N 0.189755 0.039746 TxTGKT CcCCHH 27.3 0.4 34.1 41.712557 1.1510e−45 1.00000 B 0.800587 0.012329 DxAGKT CcCCHH 21.3 0.1 35.9 67.148907 7.5094e−45 1.00000 B 0.593315 0.002784 GxGKTT CcCHHH 37.1 1.7 139.7 27.458764 2.4284e−38 1.00000 B 0.265569 0.012053 SxTKVD HcEEEE 55.5 12.5 313.0 12.416336 6.4044e−35 1.00000 N 0.177316 0.039921 GxGKST CcCHHH 30.9 1.2 106.0 27.358680 4.2728e−34 1.00000 B 0.291509 0.011250 VxCKNG EcCCCC 26.6 1.4 55.2 21.380843 4.0094e−27 1.00000 B 0.481884 0.025784 NxKVDK CeEEEE 29.8 5.5 135.3 10.625194 1.1533e−25 1.00000 N 0.220251 0.040399 NxGKTT CcCHHH 15.8 0.3 24.1 29.281293 3.1531e−24 1.00000 B 0.655602 0.011790 DxGVGK CcCCCH 15.1 0.2 50.6 32.811283 3.2521e−24 1.00000 B 0.298419 0.004088 SxTGNT CcCCHH 12.5 0.1 11.0 29.987850 8.0249e−22 1.00000 B 1.136364 0.012084 SxVGKS CcCCHH 15.3 0.3 41.7 26.658271 8.7346e−22 1.00000 B 0.366906 0.007632 CxGNIC EcCCCC 7.0 0.0 12.0 95.810125 2.7036e−21 1.00000 B 0.583333 0.000444 GxGKTS CcCHHH 13.9 0.2 31.5 28.626452 4.2468e−21 1.00000 B 0.441270 0.007293 SxGIGR CcCCCH 7.5 0.0 14.7 93.158277 8.5854e−21 1.00000 B 0.510204 0.000440 YxSGRT HhCCCC 17.3 0.7 30.2 19.573147 2.6454e−20 1.00000 B 0.572848 0.024310 SxGVGR CcCCHH 7.3 0.0 18.1 67.069455 1.1733e−18 1.00000 B 0.403315 0.000653 PxWNIG CeECCC 12.3 0.1 9.3 27.472358 9.0000e−18 1.00000 B 1.322581 0.012172 GxDVVG CcCHHH 2.0 0.0 2.0 8.888636 1.0693e−17 1.00000 B 1.000000 0.024689 GxGKSA CcCHHH 14.5 0.5 50.8 20.582995 1.4756e−17 1.00000 B 0.285433 0.009233 PxGSGK CcCCCH 11.0 0.2 35.4 25.572158 2.5256e−17 1.00000 B 0.310734 0.005083 CxAGIG CcCCCC 6.3 0.0 11.9 74.862067 2.6570e−17 1.00000 B 0.529412 0.000594 HxASVA EeEECC 3.0 0.0 1.0 5.165831 1.0701e−16 1.00000 B 3.000000 0.036120 AxKGLV HhHCCC 1.0 0.0 1.0 6.244247 1.0825e−16 1.00000 B 1.000000 0.025006 YxKIHA EeCCCC 1.5 0.0 1.0 7.610023 1.0914e−16 1.00000 B 1.500000 0.016974 RxTTLD EeEEEE 1.0 0.0 1.0 7.954816 1.0930e−16 1.00000 B 1.000000 0.015557 MxYIKI CcEECC 1.5 0.0 1.0 8.335733 1.0945e−16 1.00000 B 1.500000 0.014188 LxARVK ChHHHH 1.0 0.0 1.0 8.511831 1.0951e−16 1.00000 B 1.000000 0.013614 RxLFLE CcCHHH 1.0 0.0 1.0 9.594150 1.0983e−16 1.00000 B 1.000000 0.010747 GxRDNG CcEEEE 1.0 0.0 1.0 10.319729 1.0999e−16 1.00000 B 1.000000 0.009303 LxNAGK CcCCCH 6.3 0.0 10.5 61.321730 2.2405e−16 1.00000 B 0.600000 0.001003 DxGTGK CcCCCH 8.0 0.1 29.0 35.088156 4.0490e−16 1.00000 B 0.275862 0.001773 SxGIGR CcCCHH 5.9 0.0 20.2 84.110847 1.3990e−15 1.00000 B 0.292079 0.000243 AxGKTT CcCHHH 9.0 0.1 21.6 23.820242 7.2402e−15 1.00000 B 0.416667 0.006448 MxLCTL EeCCCC 7.0 0.1 9.1 26.549827 5.6450e−14 1.00000 B 0.769231 0.007547 KxVACK EeECCC 15.3 1.2 42.0 13.180952 1.8560e−13 1.00000 B 0.364286 0.028111 QxSGKT CcCCHH 7.2 0.1 17.0 26.686569 3.5476e−13 1.00000 B 0.423529 0.004215 QxGSCW CcCCHH 6.1 0.0 20.2 34.553496 4.6995e−13 1.00000 B 0.301980 0.001530 SxSGKS CcCCHH 7.7 0.1 21.4 26.468945 5.2665e−13 1.00000 B 0.359813 0.003885 MxTFKF HcCCCE 7.5 0.1 10.7 24.027808 5.5753e−13 1.00000 B 0.700935 0.008955 GxTGKT CcCCHH 8.0 0.1 30.9 22.029457 6.1861e−13 1.00000 B 0.258900 0.004149 GxGIMS CcCHHH 5.0 0.0 5.0 36.561607 7.1860e−13 1.00000 B 1.000000 0.003726 NxTPNR HhCHHH 13.8 1.0 46.4 13.288369 1.7188e−12 1.00000 B 0.297414 0.020563 VxHGKT CcCCHH 6.5 0.0 27.3 30.546954 3.0058e−12 1.00000 B 0.238095 0.001638 CxAGVG CcCCCH 5.8 0.0 17.8 40.693813 3.0166e−12 1.00000 B 0.325843 0.001135 AxGVGK CcCCCH 7.6 0.1 31.0 23.748136 3.6395e−12 1.00000 B 0.245161 0.003228 SxGACW CcECHH 5.2 0.0 4.0 53.110192 4.0212e−12 1.00000 B 1.300000 0.001416 AxNGDS CcCCCC 5.0 0.0 6.0 33.087901 4.6504e−12 1.00000 B 0.833333 0.003786 DxGKTT CcCHHH 9.5 0.3 35.5 17.343265 4.7098e−12 1.00000 B 0.267606 0.008017 LxNICR CcCCCH 4.0 0.0 7.8 61.829719 5.0603e−12 1.00000 B 0.512821 0.000536 CxAGIG CcCCCH 4.5 0.0 9.7 64.816014 5.4850e−12 1.00000 B 0.463918 0.000496 GxGKSS CcCHHH 9.7 0.3 34.0 16.497208 9.1680e−12 1.00000 B 0.285294 0.009588 IxNYTP EcCCCC 9.6 0.3 47.0 16.379090 1.5314e−11 1.00000 B 0.204255 0.006873 NxACKN EeCCCC 13.3 1.1 43.0 11.980088 1.8020e−11 1.00000 B 0.309302 0.024858 NxGSGK CcCCCH 4.0 0.0 4.0 42.938701 2.1963e−11 1.00000 B 1.000000 0.002165 QxGTGK CcCCCH 7.5 0.1 16.1 19.678453 2.2578e−11 1.00000 B 0.465839 0.008763 LxVGMV CeEEEE 3.3 0.0 7.0 117.793861 3.4484e−11 1.00000 B 0.471429 0.000112 YxDNFQ CcCCCC 6.8 0.1 15.8 22.244783 5.4167e−11 1.00000 B 0.430380 0.005790 TxCGVH CcEEEE 5.3 0.0 4.0 36.267536 8.4493e−11 1.00000 B 1.325000 0.003032 GxGKSN CcCHHH 6.3 0.1 13.0 21.117590 1.0495e−10 1.00000 B 0.484615 0.006703 DxHDIG CcCCHH 6.0 0.1 6.8 17.457699 1.1976e−10 1.00000 B 0.882353 0.016997 RxRPFN EeCCCC 7.5 0.1 6.0 16.071908 1.3686e−10 1.00000 B 1.250000 0.022701 NxSGKS CcCCHH 5.0 0.0 13.1 25.781208 2.4284e−10 1.00000 B 0.381679 0.002837 GxGKSC CcCHHH 8.5 0.3 19.8 14.494190 2.4906e−10 1.00000 B 0.429293 0.016339 LxGAGK CcCCCH 6.5 0.1 15.9 19.909508 2.8421e−10 1.00000 B 0.408805 0.006534 TxSGKT CcCCHH 10.5 0.6 48.6 12.584345 3.0343e−10 1.00000 B 0.216049 0.012838 RxVNYT EeCCCC 9.1 0.5 22.1 12.656039 3.5603e−10 1.00000 B 0.411765 0.021478 GxVGKS CcCCHH 9.1 0.4 55.2 13.436593 3.7410e−10 1.00000 B 0.164855 0.007617 TxNIGE EeCCCE 6.3 0.2 6.3 14.647106 7.3598e−10 1.00000 B 1.000000 0.028528 PxVGKS CcCCHH 7.5 0.2 26.5 15.812094 7.6266e−10 1.00000 B 0.283019 0.008077 KxYRME CcCCCC 7.4 0.2 16.0 15.025400 8.0890e−10 1.00000 B 0.462500 0.014437 GxGLGR CcCHHH 7.0 0.1 5.0 17.703901 9.5454e−10 1.00000 B 1.400000 0.015702 QxQGIM CcCCHH 4.8 0.0 5.0 28.122826 1.1237e−09 1.00000 B 0.960000 0.005790 KxQSPQ HhCCCC 5.2 0.1 7.1 20.111796 1.2579e−09 1.00000 B 0.732394 0.009265 QxRGYG CcCCHH 6.8 0.2 9.1 15.336532 1.4944e−09 1.00000 B 0.747253 0.020849 NxGKST CcCHHH 8.0 0.4 22.7 12.520330 2.0100e−09 1.00000 B 0.352423 0.016606 GxGKTF CcCHHH 8.0 0.4 17.8 12.110334 2.1948e−09 1.00000 B 0.449438 0.022622 SxVGKT CcCCHH 6.0 0.1 21.0 16.640878 2.2754e−09 1.00000 B 0.285714 0.005970 NxFCGS CcEEEC 5.5 0.1 5.0 15.478503 3.5703e−09 1.00000 B 1.100000 0.020443 NxFTVA HcCCHH 6.3 0.2 8.1 14.131219 3.6966e−09 1.00000 B 0.777778 0.023628 GxTVEK CeEEEE 13.1 1.6 41.1 9.138482 3.7062e−09 1.00000 B 0.318735 0.039863 WxHGYA CcCCHH 5.0 0.0 4.0 22.521458 3.7482e−09 1.00000 B 1.250000 0.007824 KxKACH HcCCCC 5.0 0.1 5.0 14.885519 5.2330e−09 1.00000 B 1.000000 0.022067 KxSQQK EeCCCC 6.0 0.0 4.0 20.959247 6.6296e−09 1.00000 B 1.500000 0.009023 ExTFPD CcCCCC 8.6 0.6 14.0 10.957842 6.6646e−09 1.00000 B 0.614286 0.040051 VxFTFP CcCCCC 8.6 0.6 14.0 10.948237 6.7483e−09 1.00000 B 0.614286 0.040115 VxWGRG EeECCC 4.6 0.0 5.3 23.040320 8.8272e−09 1.00000 B 0.867925 0.007448 GxGYAT CcCHHH 5.0 0.0 4.0 20.181971 8.9445e−09 1.00000 B 1.250000 0.009725 IxGSGK CcCCCH 4.0 0.0 6.0 22.389604 1.1417e−08 1.00000 B 0.666667 0.005264 DxRETG EeEECC 12.2 1.5 48.0 8.975496 1.4213e−08 1.00000 B 0.254167 0.030697 GxGKGT CcCHHH 10.2 1.0 37.7 9.601553 1.9441e−08 1.00000 B 0.270557 0.025246 SxGAGK CcCCCH 4.6 0.0 7.0 21.675509 2.2554e−08 1.00000 B 0.657143 0.006351 VxGYGT CcCHHH 5.8 0.2 6.1 13.788700 2.4146e−08 1.00000 B 0.950820 0.028106 SxKPLY CcCCCC 8.6 0.7 16.0 10.023813 3.1924e−08 1.00000 B 0.537500 0.040940 HxDHGK CcCCCH 5.0 0.1 33.0 16.457663 3.2287e−08 1.00000 B 0.151515 0.002705 QxRGLG CcCCHH 5.0 0.1 7.0 14.024044 3.4288e−08 1.00000 B 0.714286 0.017585 GxGFSI EcCEEE 4.0 0.1 4.4 17.653767 3.6548e−08 1.00000 B 0.909091 0.011507 IxGNSA HhCCHH 5.0 0.2 5.0 12.190063 3.6553e−08 1.00000 B 1.000000 0.032553

TABLE 28 In Expected in P-Value P-Value Observed Null Sequence Structure Epitopes Epi In PDB Z-Score Upper Lower Distribution Ratio Probability GLxxxQ CCchhH 54.6 10.0 239.5 14.376318 3.6957e−46 1.00000 N 0.227975 0.041884 EVxxxW CCchhH 23.1 0.5 25.5 31.732726 8.9916e−37 1.00000 B 0.905882 0.020272 GIxxxQ CCchhH 44.1 8.5 170.0 12.547464 1.8680e−35 1.00000 N 0.259412 0.049891 STxxxK CEeeeE 68.0 18.7 273.9 11.805445 7.5425e−32 1.00000 N 0.248266 0.068310 LSxxxH HHhhhH 34.7 6.5 227.6 11.162649 2.8341e−28 1.00000 N 0.152460 0.028772 GSxxxT CCchhH 36.4 3.6 141.4 17.566235 8.1592e−26 1.00000 B 0.257426 0.025327 NPxxxE CCchhH 30.1 5.6 135.5 10.539187 2.7481e−25 1.00000 N 0.222140 0.041521 GLxxxE CCchhH 55.6 15.7 370.9 10.286605 1.5314e−24 1.00000 N 0.149906 0.042345 TQxxxT CCcchH 18.0 0.7 24.5 21.679320 1.1385e−23 1.00000 B 0.734694 0.026840 GFxxxD CCchhH 35.3 7.7 175.1 10.141682 1.1664e−23 1.00000 N 0.201599 0.044152 GGxxxN CCchhH 27.3 5.1 106.7 10.105386 2.5924e−23 1.00000 N 0.255858 0.047587 CSxxxG CCcccH 11.6 0.1 36.9 42.938111 5.1216e−22 1.00000 B 0.314363 0.001957 VAxxxG ECcccC 36.9 5.0 129.3 14.592371 8.2210e−22 1.00000 B 0.285383 0.038494 LPxxxR CChhhH 31.2 6.7 201.9 9.644138 1.7359e−21 1.00000 N 0.154532 0.033103 SLxxxE CCchhH 36.6 9.3 220.9 9.134791 1.5180e−19 1.00000 N 0.165686 0.042167 GVxxxE CCchhH 38.3 10.2 238.7 8.992735 5.1079e−19 1.00000 N 0.160452 0.042731 KExxxA CCchhH 25.3 5.2 85.5 9.049696 5.5135e−19 1.00000 N 0.295906 0.061241 CKxxxT CCcccC 29.6 3.7 96.1 13.675704 1.2906e−18 1.00000 B 0.308012 0.038755 LSxxxQ CChhhH 25.1 5.2 186.8 8.904430 1.9586e−18 1.00000 N 0.134368 0.027613 TGxxxT CCcchH 26.5 5.8 112.2 8.834358 3.3175e−18 1.00000 N 0.236185 0.051631 LSxxxR CChhhH 40.4 11.5 293.2 8.662063 8.5519e−18 1.00000 N 0.137790 0.039389 DLxxxE CCchhH 30.3 7.4 187.5 8.615766 1.7599e−17 1.00000 N 0.161600 0.039316 FSxxxY HHcccH 1.1 0.1 1.0 4.074728 1.0472e−16 1.00000 B 1.100000 0.056807 NMxxxE CCchhH 27.0 3.8 79.7 12.253842 1.9659e−16 1.00000 B 0.338770 0.047324 LTxxxR CChhhH 30.4 7.8 203.9 8.238198 3.9476e−16 1.00000 N 0.149093 0.038329 YAxxxT HHcccC 20.8 2.0 55.2 13.691929 4.2721e−16 1.00000 B 0.376812 0.035555 LTxxxK CChhhH 29.4 7.5 198.1 8.183120 6.3961e−16 1.00000 N 0.148410 0.037688 QSxxxL EEcceE 30.2 7.8 260.2 8.169296 6.9027e−16 1.00000 N 0.116065 0.029863 ERxxxD HHhheC 16.2 1.0 36.2 15.054070 8.6591e−16 1.00000 B 0.447514 0.028832 LDxxxR CChhhH 32.5 8.9 240.5 8.068869 1.4172e−15 1.00000 N 0.135135 0.036966 TKxxxC CChhhH 11.0 0.5 12.0 14.531388 1.8514e−14 1.00000 B 0.916667 0.045202 CExxxY EEcccC 17.7 1.5 50.9 13.362872 2.0202e−14 1.00000 B 0.347741 0.029713 SWxxxC EEcccC 15.5 0.9 140.2 15.144607 2.9263e−14 1.00000 B 0.110556 0.006644 SAxxxR CHhhhH 38.1 12.2 224.6 7.644138 3.2710e−14 1.00000 N 0.169635 0.054175 VQxxxS ECcccC 25.7 6.6 164.8 7.619327 5.8468e−14 1.00000 N 0.155947 0.039850 NLxxxD CCchhH 24.9 6.2 242.5 7.619062 6.0600e−14 1.00000 N 0.102680 0.025522 ELxxxE CCchhH 27.3 7.3 172.9 7.544366 9.5073e−14 1.00000 N 0.157895 0.042349 GVxxxA CCchhH 27.9 4.8 176.5 10.653267 1.3946e−13 1.00000 B 0.158074 0.027331 YHxxxE HHhhhH 23.2 5.7 128.6 7.516035 1.4229e−13 1.00000 N 0.180404 0.044191 TVxxxE CHhhhH 24.2 6.2 110.1 7.404460 3.0474e−13 1.00000 N 0.219800 0.056658 SAxxxR CCcchH 16.6 1.4 68.1 12.837428 3.2464e−13 1.00000 B 0.243759 0.020953 PTxxxG CEeccC 16.5 1.4 85.8 12.894317 4.0322e−13 1.00000 B 0.192308 0.016258 QTxxxK CCcccH 14.2 1.0 50.3 13.307139 6.6972e−13 1.00000 B 0.282306 0.019950 TKxxxK EEeeeE 67.0 29.5 480.9 7.130159 9.9543e−13 1.00000 N 0.139322 0.061317 GAxxxT CCchhH 26.4 4.7 165.8 10.161537 1.2729e−12 1.00000 B 0.159228 0.028319 LSxxxK CChhhH 29.4 8.7 241.0 7.163028 1.3727e−12 1.00000 N 0.121992 0.036016 GYxxxN CEchhH 14.0 1.1 42.3 12.536419 1.6774e−12 1.00000 B 0.330969 0.025738 NTxxxK CEeeeE 33.8 11.0 168.6 7.116682 1.6931e−12 1.00000 N 0.200474 0.065182 DNxxxP CChhhH 5.3 0.0 5.0 32.897939 2.0566e−12 1.00000 B 1.060000 0.004599 WLxxxH HHcccC 15.4 1.4 51.8 12.142070 2.2839e−12 1.00000 B 0.297297 0.026471 RAxxxR HHhhhH 62.9 27.3 536.8 6.997202 2.6193e−12 1.00000 N 0.117176 0.050836 EAxxxE HHhhhH 84.2 40.9 815.1 6.937320 3.5127e−12 1.00000 N 0.103300 0.050228 GLxxxI ECceeE 9.7 0.4 17.7 15.497102 8.0689e−12 1.00000 B 0.548023 0.020915 ACxxxS CCcccC 19.1 2.5 123.5 10.614314 8.2065e−12 1.00000 B 0.154656 0.020220 GVxxxD CCchhH 23.4 6.3 189.3 6.927950 8.7577e−12 1.00000 N 0.123613 0.033287 LSxxxI CChhhH 25.4 7.1 404.3 6.907684 9.1681e−12 1.00000 N 0.062825 0.017623 QTxxxK HHhhhH 25.6 7.4 144.0 6.832254 1.5255e−11 1.00000 N 0.177778 0.051705 SSxxxD HCeeeE 41.2 15.6 216.6 6.724105 2.1591e−11 1.00000 N 0.190212 0.072065 GVxxxQ CCehhH 10.9 0.6 9.5 11.942747 2.4637e−11 1.00000 B 1.147368 0.062447 NAxxxQ HHhhhH 20.6 5.3 129.5 6.788754 2.5681e−11 1.00000 N 0.159073 0.040908 CHxxxR HHhhhC 11.0 0.9 14.0 10.896171 2.8578e−11 1.00000 B 0.785714 0.065457 GVxxxS CCchhH 21.8 3.7 118.3 9.593989 3.8268e−11 1.00000 B 0.184277 0.031117 GRxxxE CCchhH 25.7 7.7 147.8 6.680390 4.1501e−11 1.00000 N 0.173884 0.051943 PGxxxL CChhhC 18.3 2.5 95.4 10.049115 5.2259e−11 1.00000 B 0.191824 0.026518 SAxxxK CHhhhH 30.0 9.9 163.6 6.620898 5.3547e−11 1.00000 N 0.183374 0.060226 AAxxxT CCchhH 14.1 1.4 47.8 10.751572 7.3154e−11 1.00000 B 0.294979 0.029943 FPxxxT HHhhhH 22.4 4.2 81.3 9.076903 7.4347e−11 1.00000 B 0.275523 0.052004 RExxxR HHhhhH 94.3 50.1 805.4 6.456703 8.6412e−11 1.00000 N 0.117085 0.062155 HLxxxH CCcchH 10.0 0.6 18.2 12.034072 9.4334e−11 1.00000 B 0.549451 0.034515 EFxxxD EEchhH 6.7 0.1 18.7 21.811739 1.0142e−10 1.00000 B 0.358289 0.004932 SGxxxD EEeccE 50.1 21.4 292.4 6.445800 1.1982e−10 1.00000 N 0.171341 0.073174 FTxxxN CChhhH 10.0 0.6 19.8 12.030980 1.2267e−10 1.00000 B 0.505051 0.031658 RIxxxQ CCchhH 14.1 1.5 60.7 10.622272 1.3315e−10 1.00000 B 0.232290 0.023928 QCxxxH HHhhhH 13.0 1.3 29.3 10.304706 1.5452e−10 1.00000 B 0.443686 0.045783 GFxxxG CEeeeE 11.7 0.8 72.6 12.120611 2.1618e−10 1.00000 B 0.161157 0.011234 CLxxxC ECcccC 6.5 0.1 11.0 19.364662 2.2273e−10 1.00000 B 0.590909 0.009999 TCxxxH HHhhhH 10.8 0.7 27.1 11.927434 2.8064e−10 1.00000 B 0.398524 0.027021 TAxxxE CHhhhH 29.1 9.8 179.3 6.350328 3.0867e−10 1.00000 N 0.162298 0.054574 PTxxxL CChhhH 23.0 6.7 322.9 6.377182 3.1697e−10 1.00000 N 0.071229 0.020700 LDxxxK ECcccH 8.5 0.4 15.3 13.692060 3.4070e−10 1.00000 B 0.555556 0.023649 AExxxV HHhhcC 21.2 3.9 171.0 8.898036 3.9391e−10 1.00000 B 0.123977 0.022677 KCxxxH HCcccC 10.6 0.8 22.5 11.558959 4.2767e−10 1.00000 B 0.471111 0.033381 LHxxxL HHhhcC 15.1 2.0 43.7 9.474868 4.3344e−10 1.00000 B 0.345538 0.045826 EAxxxQ HHhhhH 45.2 18.8 422.8 6.237266 4.7014e−10 1.00000 N 0.106906 0.044414 SPxxxS ECceeE 38.1 14.9 211.2 6.241420 5.0762e−10 1.00000 N 0.180398 0.070475 TPxxxK CHhhhH 42.6 17.4 322.0 6.202797 6.0232e−10 1.00000 N 0.132298 0.054102 GAxxxE CCchhH 24.1 7.5 181.1 6.195949 9.3108e−10 1.00000 N 0.133076 0.041378 SGxxxS CCcchH 29.0 10.1 190.4 6.139692 1.1318e−09 1.00000 N 0.152311 0.052802 EGxxxE CCchhH 22.3 6.7 113.1 6.173709 1.1489e−09 1.00000 N 0.197171 0.059666 GIxxxE CCchhH 25.4 8.2 190.6 6.143827 1.2211e−09 1.00000 N 0.133263 0.042994 GQxxxK CCchhH 15.4 2.3 38.6 8.950992 1.3046e−09 1.00000 B 0.398964 0.059134 DSxxxR HHhhhH 25.5 8.4 161.5 6.050940 2.1286e−09 1.00000 N 0.157895 0.052091 FPxxxA CCchhH 15.2 2.1 79.8 9.135392 2.2216e−09 1.00000 B 0.190476 0.026431 GExxxQ CCchhH 16.3 2.6 51.0 8.660100 2.2929e−09 1.00000 B 0.319608 0.051527 TQxxxS EEeccE 26.8 9.1 251.1 6.004098 2.6913e−09 1.00000 N 0.106730 0.036075 SAxxxR CCcccH 11.7 1.1 36.6 10.133488 2.8456e−09 1.00000 B 0.319672 0.030705 DKxxxP HHhccC 19.5 5.7 86.1 6.017973 3.3049e−09 1.00000 N 0.226481 0.065745 KLxxxE CCchhH 27.3 9.4 234.8 5.963685 3.3721e−09 1.00000 N 0.116269 0.040002 GIxxxT CCchhH 22.5 5.0 143.4 7.993685 3.5299e−09 1.00000 B 0.156904 0.034712

TABLE 29 In Expected in P-Value P-Value Observed Null Sequence Structure Epitopes Epi In PDB Z-Score Upper Lower Distribution Ratio Probability STxxDK CEeeEE 59.1 14.2 254.5 12.233583 5.4622e−34 1.00000 N 0.232220 0.055962 SAxxGR CCccHH 15.6 0.1 46.1 49.079185 2.2129e−29 1.00000 B 0.338395 0.002168 TKxxKK EEeeEE 66.1 19.3 341.6 10.992116 7.5992e−28 1.00000 N 0.193501 0.056354 TQxxKT CCccHH 15.3 0.2 14.3 29.339724 1.6806e−25 1.00000 B 1.069930 0.016341 ERxxMD HHhhEC 15.1 0.2 36.2 30.598992 8.7736e−24 1.00000 B 0.417127 0.006560 PTxxIG CEecCC 14.3 0.2 12.4 30.481402 5.0639e−23 1.00000 B 1.153226 0.013170 SAxxGR CCccCH 11.7 0.1 21.6 43.188076 9.9068e−23 1.00000 B 0.541667 0.003367 LSxxYH HHhhHH 26.5 2.5 52.5 15.583360 4.0718e−21 1.00000 B 0.504762 0.047463 GSxxST CCchHH 17.9 0.8 49.1 19.913960 7.6094e−20 1.00000 B 0.364562 0.015335 YAxxRT HHccCC 18.3 1.0 30.1 17.537770 1.2259e−19 1.00000 B 0.607973 0.033422 CSxxIG CCccCC 8.5 0.0 12.3 52.662194 1.3010e−19 1.00000 B 0.691057 0.002110 TGxxKT CCccHH 24.5 2.2 85.8 15.179670 9.8763e−19 1.00000 B 0.285548 0.025790 TExxSI HHhcCC 3.0 0.1 2.0 7.770443 1.3782e−17 1.00000 B 1.500000 0.032062 CSxxVG CCccCH 6.8 0.0 16.0 77.222504 2.0499e−17 1.00000 B 0.425000 0.000484 QSxxSL EEccEE 25.0 5.4 183.2 8.519344 5.1349e−17 1.00000 N 0.136463 0.029668 NAxxQV CCchHH 1.0 0.0 1.0 4.478223 1.0575e−16 1.00000 B 1.000000 0.047496 QLxxRQ HHhhCC 1.0 0.0 1.0 5.045279 1.0683e−16 1.00000 B 1.000000 0.037800 ERxxAM CCccCC 1.0 0.0 1.0 5.111929 1.0693e−16 1.00000 B 1.000000 0.036857 LLxxDN HHhhHC 1.0 0.0 1.0 5.969702 1.0799e−16 1.00000 B 1.000000 0.027295 DDxxFV CCccCE 1.0 0.0 1.0 6.356999 1.0834e−16 1.00000 B 1.000000 0.024148 GSxxAE CEecCE 1.0 0.0 1.0 7.378896 1.0902e−16 1.00000 B 1.000000 0.018035 ITxxVF ECccEE 1.0 0.0 1.0 8.484434 1.0950e−16 1.00000 B 1.000000 0.013701 SSxxVD HCeeEE 40.7 12.3 215.6 8.311402 1.6093e−16 1.00000 N 0.188776 0.057261 QGxxLG CCccHH 9.0 0.2 9.3 21.852434 4.1091e−16 1.00000 B 0.967742 0.017891 RIxxNL HHhhHH 16.5 1.0 44.0 15.841191 4.4922e−16 1.00000 B 0.375000 0.022308 CHxxYR HHhhHC 10.0 0.3 10.0 17.416672 1.0961e−15 1.00000 B 1.000000 0.031914 VAxxNG ECccCC 21.6 2.4 46.6 12.569376 1.5977e−15 1.00000 B 0.463519 0.052575 LDxxGK CCccCH 11.3 0.3 39.1 20.968186 2.4107e−15 1.00000 B 0.289003 0.007117 SWxxGC EEccCC 15.3 0.8 129.4 15.971916 6.7763e−15 1.00000 B 0.118238 0.006387 SGxxKS CCccHH 20.0 2.0 75.4 12.863878 7.1564e−15 1.00000 B 0.265252 0.026650 WKxxFT HHhcCC 9.4 0.2 14.5 22.543920 7.4766e−15 1.00000 B 0.648276 0.011698 QTxxGK CCccCH 13.5 0.6 41.8 16.189713 2.0888e−14 1.00000 B 0.322967 0.015328 NTxxDK CEeeEE 28.8 7.8 135.9 7.708178 2.6509e−14 1.00000 N 0.211921 0.057719 RMxxFK HHccCC 9.5 0.2 10.7 18.948412 2.7945e−14 1.00000 B 0.887850 0.022821 KCxxCH HCccCC 10.6 0.4 12.6 17.091511 2.8775e−14 1.00000 B 0.841270 0.029296 LGxxIV CCeeEE 9.3 0.2 37.1 21.972185 8.4861e−14 1.00000 B 0.250674 0.004672 CLxxIC ECccCC 6.0 0.0 9.0 35.053684 9.5349e−14 1.00000 B 0.666667 0.003234 YHxxNE HHhhHH 19.5 2.4 46.3 11.422064 2.0039e−13 1.00000 B 0.421166 0.051197 LVxxHE HHhhHH 8.9 0.1 52.2 23.129204 2.5855e−13 1.00000 B 0.170498 0.002753 IVxxTP ECccCC 9.3 0.2 23.0 19.542690 3.1552e−13 1.00000 B 0.404348 0.009480 LDxxGK ECccCH 7.3 0.1 6.4 28.478746 3.3239e−13 1.00000 B 1.140625 0.007829 GKxxAH CHhhHH 10.0 0.4 9.1 14.125237 6.7470e−13 1.00000 B 1.098901 0.043619 DNxxKT CCccHH 10.3 0.4 16.6 15.371814 9.7383e−13 1.00000 B 0.620482 0.025519 CSxxIG CCccCH 4.8 0.0 11.4 73.811659 1.4691e−12 1.00000 B 0.421053 0.000370 ATxxRV CCchHH 8.3 0.2 7.7 19.415438 1.7742e−12 1.00000 B 1.077922 0.020018 QCxxCH HHhhHH 13.0 1.0 22.0 12.026076 1.9167e−12 1.00000 B 0.590909 0.047197 DGxxGK CCccCH 15.5 1.3 97.0 12.448014 2.8267e−12 1.00000 B 0.159794 0.013569 ACxxDS CCccCC 9.1 0.2 75.1 18.214718 3.0063e−12 1.00000 B 0.121172 0.003162 GSxxTT CCchHH 11.2 0.6 31.0 14.187378 4.0789e−12 1.00000 B 0.361290 0.018443 LGxxCR CCccCH 5.5 0.0 10.3 37.032677 6.6138e−12 1.00000 B 0.533981 0.002129 GTxxTF CCchHH 8.0 0.2 12.8 16.365802 1.0631e−11 1.00000 B 0.625000 0.017934 SSxxNT CCccHH 7.0 0.1 6.5 21.121389 1.2770e−11 1.00000 B 1.076923 0.014361 AAxxTT CCchHH 9.0 0.3 18.3 14.828063 1.6044e−11 1.00000 B 0.491803 0.018968 NAxxTT CCchHH 9.3 0.3 26.0 15.589019 1.7742e−11 1.00000 B 0.357692 0.012886 SPxxLS ECceEE 30.0 9.7 170.2 6.744862 2.3659e−11 1.00000 N 0.176263 0.056698 GVxxSA CCchHH 13.4 1.1 67.0 12.144064 2.4899e−11 1.00000 B 0.200000 0.015680 FPxxLT HHhhHH 19.4 3.0 59.9 9.792754 2.7723e−11 1.00000 B 0.323873 0.049478 KNxxCK EEecCC 13.7 1.2 42.0 11.504674 3.8780e−11 1.00000 B 0.326190 0.028883 DSxxGK CCccCH 11.3 0.7 45.5 12.872679 4.9903e−11 1.00000 B 0.248352 0.015161 PGxxAL CChhHC 10.3 0.7 15.5 11.892512 7.8512e−11 1.00000 B 0.664516 0.044128 PSxxGK CCccCH 8.0 0.2 33.5 15.968086 8.7729e−11 1.00000 B 0.238806 0.007104 QGxxKT CCccHH 6.2 0.1 11.9 20.953421 9.3677e−11 1.00000 B 0.521008 0.007207 AKxxNF CCccCE 7.3 0.2 20.8 18.084245 9.7158e−11 1.00000 B 0.350962 0.007557 NDxxGG CChhHC 8.6 0.4 12.7 14.018717 1.3495e−10 1.00000 B 0.677165 0.028017 RIxxYT EEccCC 9.0 0.4 49.0 13.900228 1.8474e−10 1.00000 B 0.183673 0.007898 DAxxKT CCccHH 9.0 0.4 20.0 12.940407 1.8643e−10 1.00000 B 0.450000 0.022343 HHxxLP EEeeCC 4.4 0.0 9.4 41.428721 1.9001e−10 1.00000 B 0.468085 0.001195 VSxxCI HHccCH 4.0 0.0 6.0 36.564258 2.3293e−10 1.00000 B 0.666667 0.001987 PNxxGK CCccCH 7.0 0.2 25.1 16.489979 3.2368e−10 1.00000 B 0.278884 0.006877 QTxxAK HHhhHH 11.5 0.9 25.1 11.041981 3.3849e−10 1.00000 B 0.458167 0.037806 GQxxMS CCchHH 5.0 0.1 5.0 19.598731 3.5034e−10 1.00000 B 1.000000 0.012850 EAxxAE HHhhHH 21.2 4.2 95.4 8.498906 7.3395e−10 1.00000 B 0.222222 0.043919 DNxxVP CChhHH 5.3 0.0 4.0 27.167952 8.4410e−10 1.00000 B 1.325000 0.005390 QCxxCW CCecHH 4.2 0.0 9.5 34.016093 8.4522e−10 1.00000 B 0.442105 0.001596 MExxTL EEccCC 7.0 0.3 9.1 13.024031 8.9179e−10 1.00000 B 0.769231 0.030212 QCxxCW CCccHH 4.8 0.0 20.2 33.654743 1.0099e−09 1.00000 B 0.237624 0.001000 GLxxWK EEccCC 6.2 0.1 13.4 16.284448 2.1044e−09 1.00000 B 0.462687 0.010444 TVxxNE CHhhHH 8.8 0.6 11.6 11.143008 2.1359e−09 1.00000 B 0.758621 0.049430 QVxxYG CCccHH 6.8 0.2 7.1 13.693903 2.2761e−09 1.00000 B 0.957746 0.033465 NQxxNR HHchHH 12.9 1.5 47.3 9.598831 2.8315e−09 1.00000 B 0.272727 0.030964 WGxxYA CCccHH 5.0 0.0 4.0 22.841046 3.3515e−09 1.00000 B 1.250000 0.007609 VQxxGS ECccCC 20.1 4.1 109.8 8.109442 3.6024e−09 1.00000 B 0.183060 0.036992 TWxxGE EEccCE 6.5 0.2 7.5 13.828612 3.7039e−09 1.00000 B 0.866667 0.028366 PGxxKG CCccHH 10.8 0.9 34.8 10.398182 4.1662e−09 1.00000 B 0.310345 0.026618 TDxxAW CChhHH 15.5 2.5 46.1 8.533841 5.0000e−09 1.00000 B 0.336226 0.053469 GAxxTT CCchHH 9.0 0.6 23.9 10.640696 5.7397e−09 1.00000 B 0.376569 0.026564 GLxxSI ECceEE 5.5 0.1 6.2 16.659221 5.8987e−09 1.00000 B 0.887097 0.017201 GVxxSN CCchHH 6.3 0.2 13.0 14.762570 6.5204e−09 1.00000 B 0.484615 0.013424 SNxxNA HHhhHH 9.7 0.7 25.5 10.702628 6.6082e−09 1.00000 B 0.380392 0.028390 GYxxNF CCccCC 8.8 0.6 19.7 10.906559 1.1072e−08 1.00000 B 0.446701 0.029682 ACxxCH CChhHH 6.0 0.1 5.0 13.761477 1.1262e−08 1.00000 B 1.200000 0.025723 NAxxSD HHhhHH 9.5 0.8 17.0 9.892985 1.1291e−08 1.00000 B 0.558824 0.047657 GDxxDI CCccCH 6.0 0.2 10.7 13.237708 1.2867e−08 1.00000 B 0.560748 0.018302 NSxxTT CCchHH 6.5 0.2 9.0 13.069026 1.2875e−08 1.00000 B 0.722222 0.026213 GCxxCH CHhhCC 9.2 0.7 22.6 10.113297 1.3219e−08 1.00000 B 0.407080 0.032100 LTxxHY CEecCC 5.0 0.1 8.0 15.932022 1.3450e−08 1.00000 B 0.625000 0.011987 TCxxCH HHhhHH 8.8 0.6 17.1 10.560727 1.3572e−08 1.00000 B 0.514620 0.036390 GVxxSS CCchHH 8.0 0.5 22.6 10.763572 1.6961e−08 1.00000 B 0.353982 0.021985 MCxxAL EEchHH 5.7 0.1 5.0 13.068806 1.8614e−08 1.00000 B 1.140000 0.028442

TABLE 30 In Expected In P-Value P-Value Observed Null Sequence Structure Epitopes in Epi PDB Z-Score Upper Lower Distribution Ratio Probability STxVxK CEeEeE 64.0 12.0 256.9 15.417593 6.1069e−53 1.00000 N 0.249124 0.046526 GSxKxT CCcHhH 34.1 0.8 86.9 37.367230 5.6913e−46 1.00000 B 0.392405 0.009223 TKxDxK EEeEeE 66.5 16.5 338.4 12.643443 3.0096e−36 1.00000 N 0.196513 0.048650 TQxGxT CCcChH 18.0 0.2 17.2 35.333617 2.8357e−32 1.00000 B 1.046512 0.013590 CKxGxT CCcCcC 27.2 1.1 50.0 25.153537 9.5225e−32 1.00000 B 0.544000 0.022017 VAxKxG ECcCcC 31.1 2.2 50.4 20.175102 6.0519e−30 1.00000 B 0.617063 0.042673 CSxGxG CCcCcH 10.3 0.0 36.8 75.277474 2.5489e−25 1.00000 B 0.279891 0.000507 FPxHxA CCcHhH 11.6 0.1 14.2 36.450813 4.1020e−22 1.00000 B 0.816901 0.007059 SSxKxD HCeEeE 38.9 9.5 196.6 9.744738 4.9097e−22 1.00000 N 0.197864 0.048527 PTxNxG CEeCcC 15.5 0.1 11.5 30.180949 2.1746e−21 1.00000 B 1.347826 0.012468 AAxKxT CCcHhH 13.1 0.2 24.7 27.588401 7.5720e−21 1.00000 B 0.530364 0.008904 GAxKxT CCcHhH 18.7 0.8 60.0 20.216935 2.7607e−20 1.00000 B 0.311667 0.013248 YAxGxT HHcCcC 18.8 0.9 34.2 18.578825 3.4934e−20 1.00000 B 0.549708 0.027763 SAxIxR CCcCcH 9.7 0.0 14.7 44.440313 4.2337e−20 1.00000 B 0.659864 0.003220 NTxVxK CEeEeE 29.8 6.7 140.9 9.196737 1.1483e−19 1.00000 N 0.211498 0.047197 GVxKxS CCcHhH 14.0 0.3 41.2 23.421845 2.3634e−19 1.00000 B 0.339806 0.008322 ACxGxS CCcCcC 12.1 0.2 75.0 29.273930 2.9742e−19 1.00000 B 0.161333 0.002221 GVxKxA CCcHhH 14.4 0.4 55.7 21.200156 8.0469e−18 1.00000 B 0.258528 0.007849 LDxAxK CCcCcH 10.3 0.1 31.5 30.561504 1.0872e−17 1.00000 B 0.326984 0.003541 FKxSxF HCcCcC 1.0 0.0 1.0 5.225860 1.0710e−16 1.00000 B 1.000000 0.035324 ADxLxP EEcCcC 1.7 0.0 1.0 6.058130 1.0808e−16 1.00000 B 1.700000 0.026525 ASxNxY CEhHhH 1.0 0.0 1.0 6.128737 1.0814e−16 1.00000 B 1.000000 0.025933 EAxRxT HHcCcH 1.0 0.0 1.0 8.216078 1.0940e−16 1.00000 B 1.000000 0.014598 SAxVxR CCcChH 8.3 0.1 18.1 35.643410 1.8927e−16 1.00000 B 0.458564 0.002966 VSxGxG EEeCcC 15.7 0.7 142.8 17.308385 8.3711e−16 1.00000 B 0.109944 0.005252 GTxKxF CCcHhH 8.0 0.1 9.8 27.471521 9.4328e−16 1.00000 B 0.816327 0.008546 TGxGxT CCcChH 24.5 3.1 86.8 12.456089 1.4644e−15 1.00000 B 0.282258 0.035354 QTxTxK CCcCcH 7.5 0.1 11.0 31.920048 1.2186e−14 1.00000 B 0.681818 0.004971 MExCxL EEcCcC 7.0 0.1 9.1 27.627578 3.2583e−14 1.00000 B 0.769231 0.006976 DNxGxT CCcChH 10.3 0.3 15.9 17.812272 5.0703e−14 1.00000 B 0.647799 0.020148 RMxTxK HHcCcC 9.5 0.3 10.8 18.244981 5.8055e−14 1.00000 B 0.879630 0.024326 CLxNxC ECcCcC 6.5 0.0 10.0 38.099027 6.1079e−14 1.00000 B 0.650000 0.002893 GLxFxI ECcEeE 7.2 0.1 7.9 24.637453 8.3971e−14 1.00000 B 0.911392 0.010673 NWxRxV CHhHhH 7.3 0.1 21.0 29.076095 1.5643e−13 1.00000 B 0.347619 0.002959 SAxIxR CCcChH 7.3 0.1 20.6 28.942731 1.6267e−13 1.00000 B 0.354369 0.003045 LDxAxK ECcCcH 7.0 0.0 5.5 43.537246 2.7400e−13 1.00000 B 1.272727 0.002893 NAxKxT CCcHhH 9.3 0.2 16.7 18.667715 3.1319e−13 1.00000 B 0.556886 0.014312 SGxGxS CCcChH 20.0 2.4 84.1 11.420009 3.1854e−13 1.00000 B 0.237812 0.028966 TPxLxK CCcCcH 9.1 0.2 18.4 18.736598 3.4040e−13 1.00000 B 0.494565 0.012340 DGxTxK CCcCcH 8.0 0.1 29.0 22.438199 4.3553e−13 1.00000 B 0.275862 0.004267 NVxCxN EEcCcC 14.3 1.0 43.1 13.214649 6.2025e−13 1.00000 B 0.331787 0.023961 SSxGxT CCcChH 8.0 0.2 11.0 18.713621 7.2943e−13 1.00000 B 0.727273 0.016145 TQxPxS EEeCcE 25.8 6.9 245.4 7.260776 7.8442e−13 1.00000 N 0.105134 0.028289 GVxKxN CCcHhH 6.3 0.1 12.0 26.995054 5.1295e−12 1.00000 B 0.525000 0.004482 GGxWxF CCcEeE 5.5 0.0 12.0 37.207253 7.6246e−12 1.00000 B 0.458333 0.001810 NVxKxS CCcHhH 7.5 0.2 10.3 18.894023 1.2990e−11 1.00000 B 0.728155 0.014900 DAxGxT CCcChH 9.0 0.4 18.0 14.731130 1.7133e−11 1.00000 B 0.500000 0.019530 NSxKxT CCcHhH 6.5 0.1 9.0 21.907899 3.2501e−11 1.00000 B 0.722222 0.009615 IVxYxP ECcCcC 10.3 0.6 23.0 13.217500 4.2034e−11 1.00000 B 0.447826 0.024211 RIxNxT EEcCcC 9.0 0.3 49.0 15.035039 5.1668e−11 1.00000 B 0.183673 0.006826 KCxAxH HCcCcC 7.0 0.1 6.1 17.691757 5.5611e−11 1.00000 B 1.147541 0.019116 RLxPxE HCcChH 8.0 0.4 8.5 12.478417 6.3808e−11 1.00000 B 0.941176 0.045861 GQxIxS CCcHhH 7.0 0.2 9.0 15.467350 8.5625e−11 1.00000 B 0.777778 0.021972 GDxHxI CCcCcH 6.0 0.1 6.2 16.372862 1.4245e−10 1.00000 B 0.967742 0.021171 SWxRxC EEcCcC 4.3 0.0 5.3 36.955945 2.1112e−10 1.00000 B 0.811321 0.002545 DSxVxK CCcCcH 8.3 0.3 37.5 15.339191 2.1634e−10 1.00000 B 0.221333 0.007352 FTxAxN CChHhH 7.8 0.3 13.0 15.243971 3.2013e−10 1.00000 B 0.600000 0.019239 HHxExP EEeEcC 5.4 0.0 9.4 24.178681 3.9133e−10 1.00000 B 0.574468 0.005237 NQxPxR HHcHhH 12.9 1.3 49.2 10.416783 6.2879e−10 1.00000 B 0.262195 0.025975 RGxGxG CCcChH 11.5 1.0 29.8 10.632146 9.6622e−10 1.00000 B 0.385906 0.033823 PNxSxK CCcCcH 5.0 0.1 10.1 21.548123 1.0440e−09 1.00000 B 0.495050 0.005246 EExGxW CCcCcE 6.0 0.1 11.1 16.481972 1.1317e−09 1.00000 B 0.540541 0.011567 SPxSxS ECcEeE 19.5 5.5 115.4 6.119672 1.8049e−09 1.00000 N 0.168977 0.047638 EFxFxD CCcCcC 9.7 0.7 16.0 10.750240 2.3506e−09 1.00000 B 0.606250 0.045597 QGxGxG CCcChH 8.5 0.5 15.0 11.884559 2.5652e−09 1.00000 B 0.566667 0.031413 GTxKxT CCcHhH 9.0 0.5 53.1 11.802594 2.5828e−09 1.00000 B 0.169492 0.009815 LGxIxR CCcCcH 4.0 0.0 7.8 27.243385 3.4482e−09 1.00000 B 0.512821 0.002742 SDxAxN ECcCcC 6.0 0.2 8.0 13.656497 4.1912e−09 1.00000 B 0.750000 0.023197 KNxFxV HHcCcH 6.3 0.2 8.0 13.833088 4.5236e−09 1.00000 B 0.787500 0.024933 CSxGxG CCcCcC 8.3 0.4 31.0 12.038413 6.1081e−09 1.00000 B 0.267742 0.013971 LGxSxV CCeEeE 6.0 0.1 20.2 15.206575 6.1464e−09 1.00000 B 0.297030 0.007383 NYxPxL CCcCcC 11.1 1.1 37.6 9.595732 7.2007e−09 1.00000 B 0.295213 0.029674 SCxQxT CCcEeE 10.1 0.9 32.0 10.049367 7.2459e−09 1.00000 B 0.315625 0.027111 NRxKxT HHcCcC 14.5 2.2 44.1 8.614814 7.3085e−09 1.00000 B 0.328798 0.048936 GFxIxG CEeEeE 6.5 0.2 34.1 15.573549 8.3341e−09 1.00000 B 0.190616 0.004874 QVxGxG CCcChH 6.8 0.3 7.1 12.055621 9.8300e−09 1.00000 B 0.957746 0.042727 QRxGxG CCcChH 9.0 0.7 19.0 9.982543 9.9913e−09 1.00000 B 0.473684 0.037666 KNxAxK EEeCcC 13.7 1.9 42.0 8.661753 1.1168e−08 1.00000 B 0.326190 0.046053 QAxCxQ HHhHhC 11.3 1.2 45.4 9.439394 1.3106e−08 1.00000 B 0.248899 0.025993 STxExT EEeEeE 11.4 1.3 30.4 9.145725 1.3944e−08 1.00000 B 0.375000 0.042057 KDxRxE CCcCcC 9.8 0.8 23.0 9.956334 1.4414e−08 1.00000 B 0.426087 0.036543 GHxYxT CCcHhH 6.0 0.1 5.1 13.618973 1.5371e−08 1.00000 B 1.176471 0.026761 YRxLxV HCcEeE 5.0 0.1 5.0 13.141823 1.7633e−08 1.00000 B 1.000000 0.028136 PGxGxG CCcChH 10.8 1.1 38.1 9.489389 2.0316e−08 1.00000 B 0.283465 0.028342 RExGxS EEcCcC 11.3 1.2 49.0 9.175646 2.2602e−08 1.00000 B 0.230612 0.025193 GTxKxC CCcHhH 4.0 0.0 7.1 20.814784 2.5870e−08 1.00000 B 0.563380 0.005133 QCxSxW CCcChH 4.4 0.0 21.8 23.337447 2.8327e−08 1.00000 B 0.184874 0.001472 TAxLxL ECcCeE 3.0 0.0 4.0 33.845437 2.9972e−08 1.00000 B 0.750000 0.001958 SGxGxT CCcChH 13.9 2.1 76.1 8.298731 3.2053e−08 1.00000 B 0.182654 0.027389 KQxTxN CEeEeE 11.7 1.5 31.3 8.462380 4.9081e−08 1.00000 B 0.373802 0.048588 DKxGxP HHhCcC 15.4 2.8 61.6 7.726483 5.0446e−08 1.00000 B 0.250000 0.045292 EYxPxG CCcCcC 9.3 0.9 25.5 9.162766 7.1809e−08 1.00000 B 0.364706 0.034330 SPxLxD CCcCcC 8.4 0.6 27.7 9.963668 7.7018e−08 1.00000 B 0.303249 0.022499 QSxSxL EEcCeE 15.7 2.8 127.3 7.707213 8.1135e−08 1.00000 B 0.123331 0.022352 KMxFxL CCcCcC 6.3 0.3 12.6 11.723551 8.2273e−08 1.00000 B 0.500000 0.021454 ELxPxR CCcCcE 5.7 0.2 7.0 12.480023 1.1672e−07 1.00000 B 0.814286 0.028562 GQxGxC CCcCcH 7.0 0.4 19.7 10.157502 1.2223e−07 1.00000 B 0.355330 0.021722 TKxFxN EEeEcC 4.4 0.1 8.4 18.030242 1.2284e−07 1.00000 B 0.523810 0.006951 QGxGxT CCcChH 6.2 0.3 13.0 11.287013 1.2372e−07 1.00000 B 0.476923 0.021621

TABLE 31 In Expected In P-Value P-Value Observed Null Sequence Structure Epitopes in Epi PDB Z-Score Upper Lower Distribution Ratio Probability STxVDK CEeEEE 58.1 9.7 253.5 15.835199 1.1831e−55 1.00000 N 0.229191 0.038304 TKxDKK EEeEEE 66.1 13.1 336.4 14.928529 8.7974e−50 1.00000 N 0.196492 0.038972 SSxKVD HCeEEE 38.4 7.7 196.6 11.327509 3.8624e−29 1.00000 N 0.195320 0.038973 TQxGKT CCcCHH 15.3 0.2 14.3 32.629967 8.9626e−27 1.00000 B 1.069930 0.013253 GSxKST CCcHHH 17.9 0.3 44.0 31.715529 1.6123e−26 1.00000 B 0.406818 0.007041 SAxIGR CCcCCH 9.7 0.0 14.7 89.096764 1.6309e−25 1.00000 B 0.659864 0.000805 NTxVDK CEeEEE 28.8 5.4 135.9 10.341170 2.2370e−24 1.00000 N 0.211921 0.039382 YAxGRT HHcCCC 18.3 0.7 30.1 21.449600 1.5545e−22 1.00000 B 0.607973 0.022919 CSxGIG CCcCCC 6.3 0.0 11.9 189.417992 3.9006e−22 1.00000 B 0.529412 0.000093 LDxAGK CCcCCH 10.3 0.0 30.5 47.444266 1.7930e−21 1.00000 B 0.337705 0.001534 TGxGKT CCcCHH 24.5 1.7 83.7 17.637210 2.4487e−21 1.00000 B 0.292712 0.020372 SAxVGR CCcCHH 8.3 0.0 18.1 71.080806 3.2725e−21 1.00000 B 0.458564 0.000751 SGxGKS CCcCHH 20.0 1.1 73.1 18.620112 3.0285e−20 1.00000 B 0.273598 0.014374 PTxNIG CEeCCC 14.3 0.1 10.3 28.371217 1.6378e−19 1.00000 B 1.388350 0.012635 SAxIGR CCcCHH 7.3 0.0 20.0 71.573397 5.4679e−19 1.00000 B 0.365000 0.000519 GTxVVG CCcHHH 2.0 0.0 2.0 11.343455 6.6929e−18 1.00000 B 1.000000 0.015305 VAxKNG ECcCCC 20.6 1.6 43.0 15.114508 7.1138e−18 1.00000 B 0.479070 0.038057 GVxKSA CCcHHH 12.4 0.2 44.6 24.691608 9.2568e−18 1.00000 B 0.278027 0.005464 ACxGDS CCcCCC 9.1 0.1 72.0 37.337944 1.1616e−17 1.00000 B 0.126389 0.000815 DNxGKT CCcCHH 10.3 0.1 15.9 26.867787 1.8321e−17 1.00000 B 0.647799 0.009068 RSxFLE CCcHHH 1.0 0.0 1.0 5.834083 1.0785e−16 1.00000 B 1.000000 0.028542 GTxKPV CCcCCE 1.7 0.0 1.0 6.259571 1.0826e−16 1.00000 B 1.700000 0.024887 ASxNTY CEhHHH 1.0 0.0 1.0 6.291002 1.0829e−16 1.00000 B 1.000000 0.024645 YIxIHA EEcCCC 1.5 0.0 1.0 6.690226 1.0860e−16 1.00000 B 1.500000 0.021854 DDxRFV CCcCCE 1.0 0.0 1.0 7.147748 1.0889e−16 1.00000 B 1.000000 0.019197 GYxDNG CCeEEE 1.0 0.0 1.0 19.741459 1.1074e−16 1.00000 B 1.000000 0.002559 DGxTGK CCcCCH 8.0 0.0 29.0 37.332124 1.5231e−16 1.00000 B 0.275862 0.001568 GSxKTT CCcHHH 11.2 0.2 31.0 23.154082 1.8616e−16 1.00000 B 0.361290 0.007299 NAxKTT CCcHHH 9.3 0.1 14.1 26.923386 2.8401e−16 1.00000 B 0.659574 0.008319 CSxGVG CCcCCH 5.8 0.0 16.0 101.911600 2.9554e−16 1.00000 B 0.362500 0.000202 CLxNIC ECcCCC 6.0 0.0 9.0 54.727710 4.6743e−16 1.00000 B 0.666667 0.001332 DAxGKT CCcCHH 9.0 0.1 18.0 25.724945 1.1942e−15 1.00000 B 0.500000 0.006664 GTxKTF CCcHHH 8.0 0.1 9.8 25.326602 3.3955e−15 1.00000 B 0.816327 0.010033 AAxKTT CCcHHH 9.0 0.1 18.0 23.672806 5.1140e−15 1.00000 B 0.500000 0.007842 RMxTFK HHcCCC 9.5 0.2 10.7 20.171854 9.3741e−15 1.00000 B 0.887850 0.020204 LDxAGK ECcCCH 7.0 0.0 5.5 57.251217 1.7841e−14 1.00000 B 1.272727 0.001675 GAxKTT CCcHHH 9.0 0.2 17.1 21.498820 2.3496e−14 1.00000 B 0.526316 0.009963 IVxYTP ECcCCC 9.3 0.2 22.0 21.346526 6.3228e−14 1.00000 B 0.422727 0.008360 CSxGIG CCcCCH 4.5 0.0 11.4 110.094950 8.9687e−14 1.00000 B 0.394737 0.000146 QTxTGK CCcCCH 7.5 0.1 10.0 26.708621 1.0200e−13 1.00000 B 0.750000 0.007783 MExCTL EEcCCC 7.0 0.1 9.1 23.929635 2.3636e−13 1.00000 B 0.769231 0.009264 GVxKSS CCcHHH 8.0 0.1 18.1 21.088337 5.5327e−13 1.00000 B 0.441989 0.007735 GQxIMS CCcHHH 5.0 0.0 5.0 37.108769 6.1975e−13 1.00000 B 1.000000 0.003618 PNxSGK CCcCCH 5.0 0.0 10.1 43.402993 1.0258e−12 1.00000 B 0.495050 0.001309 SSxGNT CCcCHH 7.0 0.1 6.0 23.356780 1.6575e−12 1.00000 B 1.166667 0.010879 DSxVGK CCcCCH 8.3 0.2 37.5 20.844667 2.1531e−12 1.00000 B 0.221333 0.004090 LGxSIV CCeEEE 6.0 0.0 14.0 27.547447 4.1259e−12 1.00000 B 0.428571 0.003347 LGxICR CCcCCH 4.0 0.0 7.8 63.205494 4.2449e−12 1.00000 B 0.512821 0.000513 NVxCKN EEcCCC 13.3 1.0 41.0 12.198471 1.2220e−11 1.00000 B 0.309302 0.024087 GVxKSN CCcHHH 6.3 0.1 11.0 23.749628 1.9657e−11 1.00000 B 0.572727 0.006297 KNxACK EEeCCC 13.7 1.1 42.0 11.874518 1.9766e−11 1.00000 B 0.326190 0.027349 RIxNYT EEcCCC 9.0 0.3 46.0 15.336804 3.5576e−11 1.00000 B 0.195652 0.007009 QCxSCW CCcCHH 4.4 0.0 20.2 52.509392 4.3647e−11 1.00000 B 0.217822 0.000347 KCxACH HCcCCC 7.0 0.1 6.1 17.744020 5.3714e−11 1.00000 B 1.147541 0.019006 PGxGKG CCcCHH 10.8 0.6 32.8 13.331730 5.3905e−11 1.00000 B 0.329268 0.018189 VDxGKT CCcCHH 7.0 0.1 27.3 18.303355 8.7340e−11 1.00000 B 0.256410 0.005170 GDxHDI CCcCCH 6.0 0.1 6.1 16.814988 9.2109e−11 1.00000 B 0.983607 0.020432 NSxKTT CCcHHH 6.5 0.1 9.0 20.025056 9.3279e−11 1.00000 B 0.722222 0.011469 PSxSGK CCcCCH 4.0 0.0 8.0 42.041347 1.1281e−10 1.00000 B 0.500000 0.001128 NQxPNR HHcHHH 12.9 1.1 47.4 11.218153 1.4078e−10 1.00000 B 0.272152 0.023798 QGxGKT CCcCHH 6.2 0.1 12.0 19.845816 1.7918e−10 1.00000 B 0.516667 0.007948 GGxGKT CCcCHH 9.0 0.4 41.4 13.504582 2.5790e−10 1.00000 B 0.217391 0.009873 EQxVGK CCcCCH 4.0 0.0 10.0 38.073494 3.0463e−10 1.00000 B 0.400000 0.001099 SWxRGC EEcCCC 4.3 0.0 5.3 33.870887 4.2263e−10 1.00000 B 0.811321 0.003027 LSxAGK CCcCCH 4.0 0.0 4.9 30.417945 6.6469e−10 1.00000 B 0.816327 0.003511 QVxGYG CCcCHH 6.8 0.2 7.1 15.043578 7.6627e−10 1.00000 B 0.957746 0.027904 VSxGCI HHcCCH 4.0 0.0 6.0 31.335851 7.9497e−10 1.00000 B 0.666667 0.002701 HHxELP EEeECC 4.4 0.0 9.4 34.320537 8.4881e−10 1.00000 B 0.468085 0.001739 TPxLPK CCcCCH 7.5 0.2 18.0 14.918687 1.0677e−09 1.00000 B 0.416667 0.013334 ALxVPD CCcCCC 6.0 0.2 7.0 14.231812 1.5040e−09 1.00000 B 0.857143 0.024560 QAxSGL HHhHHH 3.0 0.0 8.1 55.954042 2.5977e−09 1.00000 B 0.370370 0.000354 HKxQSP HHhCCC 5.3 0.1 7.1 18.695085 2.7215e−09 1.00000 B 0.746479 0.011109 LNxGMV CEeEEE 3.3 0.0 5.0 52.849045 3.3003e−09 1.00000 B 0.660000 0.000779 KNxFTV HHcCCH 6.3 0.2 8.1 14.221970 3.4346e−09 1.00000 B 0.777778 0.023338 RGxGIG CCcCHH 6.2 0.2 9.1 14.500182 3.6936e−09 1.00000 B 0.681319 0.019340 PNxGKT CCcCHH 7.0 0.3 11.1 12.297662 3.8566e−09 1.00000 B 0.630631 0.027457 QGxGIM CCcCHH 4.8 0.0 6.0 24.626370 4.6432e−09 1.00000 B 0.800000 0.006272 WGxGYA CCcCHH 5.0 0.0 4.0 21.911256 4.6611e−09 1.00000 B 1.250000 0.008263 TGxGKS CCcCHH 8.6 0.5 26.2 12.019779 5.3272e−09 1.00000 B 0.328244 0.017795 GSxVEK CEeEEE 10.5 0.9 24.4 10.064493 5.4015e−09 1.00000 B 0.430328 0.038468 EFxFPD CCcCCC 8.6 0.5 14.0 11.100589 5.5408e−09 1.00000 B 0.614286 0.039116 VSxGRG EEeCCC 4.3 0.0 5.3 24.471776 5.5860e−09 1.00000 B 0.811321 0.005776 VExTFP CCcCCC 8.6 0.6 14.0 11.070664 5.7586e−09 1.00000 B 0.614286 0.039309 GTxKSC CCcHHH 4.0 0.0 5.1 23.127532 6.4409e−09 1.00000 B 0.784314 0.005812 SDxAGN ECcCCC 6.0 0.1 5.0 14.505782 6.7366e−09 1.00000 B 1.200000 0.023211 GAxKTS CCcHHH 4.6 0.0 6.0 24.335291 7.2209e−09 1.00000 B 0.766667 0.005899 PNxGKS CCcCHH 8.0 0.4 27.7 11.511517 8.3861e−09 1.00000 B 0.288809 0.015827 GYxDNF CCcCCC 7.8 0.4 16.8 12.300028 8.5367e−09 1.00000 B 0.464286 0.022196 GHxYAT CCcHHH 5.0 0.0 4.0 20.057804 9.3926e−09 1.00000 B 1.250000 0.009845 QAxCSQ HHhHHC 11.3 1.2 43.0 9.514827 1.0843e−08 1.00000 B 0.262791 0.027116 SPxSLS ECcEEE 19.5 4.0 104.7 7.844474 1.1598e−08 1.00000 B 0.186246 0.038586 STxAGK CCcCCH 4.6 0.0 7.1 23.102876 1.3889e−08 1.00000 B 0.647887 0.005519 YRxLVV HCcEEE 5.0 0.1 5.0 13.214477 1.6713e−08 1.00000 B 1.000000 0.027836 GLxDWK EEcCCC 5.2 0.1 9.4 16.189053 1.7939e−08 1.00000 B 0.553191 0.010670 CGxGGW CCcCHH 3.0 0.0 11.0 41.184265 1.8299e−08 1.00000 B 0.272727 0.000481 ELxPLR CCcCCE 5.7 0.2 6.0 14.252520 2.0714e−08 1.00000 B 0.950000 0.025894 GVxKTS CCcHHH 6.0 0.2 20.1 13.617286 2.1197e−08 1.00000 B 0.298507 0.009159 NGxGKS CCcCHH 6.5 0.2 21.0 13.915816 2.2105e−08 1.00000 B 0.309524 0.009836 IYxDKL EEcCEE 3.0 0.0 4.0 35.222300 2.3615e−08 1.00000 B 0.750000 0.001808

TABLE 32 In Expected In P-Value P-Value Observed Null Sequence Structure Epitopes in Epi PDB Z-Score Upper Lower Distribution Ratio Probability STKxxK CEEeeE 60.5 11.8 226.5 14.522757 3.7939e−47 1.00000 N 0.267108 0.052292 EVIxxW CCChhH 22.8 0.2 22.5 53.968344 7.7380e−47 1.00000 B 1.013333 0.007666 VACxxG ECCccC 33.4 1.2 47.1 29.574227 6.3139e−42 1.00000 B 0.709130 0.025811 GSCxxT CCChhH 36.1 1.7 102.2 26.408632 2.3179e−37 1.00000 B 0.353229 0.016864 TQTxxT CCCchH 18.0 0.3 17.0 33.543696 8.6327e−32 1.00000 B 1.058824 0.014884 TKVxxK EEEeeE 66.0 18.9 393.0 11.088342 2.6474e−28 1.00000 N 0.167939 0.048171 CSAxxG CCCccH 11.6 0.0 33.2 68.884804 1.3944e−26 1.00000 B 0.349398 0.000851 PTWxxG CEEccC 14.5 0.2 12.5 30.902724 4.3313e−23 1.00000 B 1.160000 0.012920 SAGxxR CCCchH 13.2 0.2 48.1 33.084486 6.2790e−22 1.00000 B 0.274428 0.003242 QSPxxL EECceE 30.2 6.3 250.7 9.604652 2.6407e−21 1.00000 N 0.120463 0.025266 YASxxT HHCccC 19.3 1.0 33.0 18.515875 6.1353e−21 1.00000 B 0.584848 0.030509 AAGxxT CCChhH 13.1 0.3 27.3 25.583799 7.7444e−20 1.00000 B 0.479853 0.009321 GLGxxI ECCeeE 9.7 0.1 10.7 35.901749 3.0417e−19 1.00000 B 0.906542 0.006767 SSTxxD HCEeeE 40.2 11.4 216.6 8.739729 4.4322e−18 1.00000 N 0.185596 0.052797 PGHxxL CCHhhC 11.7 0.3 13.0 21.216128 1.9065e−17 1.00000 B 0.900000 0.022743 NTKxxK CEEeeE 29.8 7.3 135.5 8.590840 2.2286e−17 1.00000 N 0.219926 0.053643 ACNxxS CCCccC 7.0 0.0 7.0 38.909066 4.3747e−17 1.00000 B 1.000000 0.004602 FHIxxI HCCccE 1.8 0.0 1.0 5.653955 1.0765e−16 1.00000 B 1.800000 0.030333 ADKxxP EECccC 1.7 0.0 1.0 5.727191 1.0774e−16 1.00000 B 1.700000 0.029585 WGDxxI CCHhhH 1.0 0.0 1.0 6.949056 1.0877e−16 1.00000 B 1.000000 0.020288 GVGxxS CCChhH 14.0 0.6 56.6 17.201557 1.3442e−15 1.00000 B 0.247350 0.010819 NPTxxE CCChhH 24.1 3.0 87.4 12.312848 1.9262e−15 1.00000 B 0.275744 0.034700 TGTxxT CCCchH 12.0 0.4 22.8 17.764571 2.0846e−15 1.00000 B 0.526316 0.018957 CKNxxT CCCccC 16.8 1.2 47.7 14.763650 3.0318e−15 1.00000 B 0.352201 0.024136 CSAxxG CCCccC 10.0 0.2 26.4 22.084450 3.3022e−15 1.00000 B 0.378788 0.007518 SWGxxC EECccC 15.5 0.8 138.2 16.002815 7.0489e−15 1.00000 B 0.112156 0.006107 NAGxxT CCChhH 9.3 0.2 15.7 22.744011 8.3544e−15 1.00000 B 0.592357 0.010387 GAGxxT CCChhH 18.9 1.7 76.7 13.170310 1.7157e−14 1.00000 B 0.246415 0.022653 GVGxxA CCChhH 14.4 0.8 63.0 15.725470 1.8748e−14 1.00000 B 0.228571 0.012086 ATNxxV CCChhH 8.3 0.2 8.4 20.963833 2.3520e−14 1.00000 B 0.988095 0.018311 FPGxxA CCChhH 11.6 0.4 23.0 17.674124 2.5125e−14 1.00000 B 0.504348 0.017749 SSTxxT CCCchH 7.0 0.1 7.1 23.407247 5.9084e−14 1.00000 B 0.985915 0.012435 TVAxxE CHHhhH 14.8 1.1 24.2 13.272042 6.4829e−14 1.00000 B 0.611570 0.046058 FTVxxN CCHhhH 9.0 0.2 11.6 17.712530 1.2155e−13 1.00000 B 0.775862 0.021503 SAGxxR CCCccH 8.5 0.1 23.1 23.814209 1.6932e−13 1.00000 B 0.367965 0.005384 VSWxxG EEEccC 13.7 0.7 132.3 15.493865 1.7679e−13 1.00000 B 0.103553 0.005344 CEGxxY EECccC 15.0 1.2 45.9 13.040250 2.4547e−13 1.00000 B 0.326797 0.025189 QTGxxK CCCccH 12.2 0.6 38.8 15.210328 3.1614e−13 1.00000 B 0.314433 0.015245 DNAxxT CCCchH 9.3 0.3 13.9 17.499545 4.8409e−13 1.00000 B 0.669065 0.019531 NWGxxV CHHhhH 7.3 0.1 21.0 26.559055 5.4139e−13 1.00000 B 0.347619 0.003537 SCQxxS CCCccC 9.4 0.2 76.8 19.969066 7.6050e−13 1.00000 B 0.122396 0.002764 KETxxA CCChhH 18.8 2.4 45.1 10.948289 1.1586e−12 1.00000 B 0.416851 0.052675 NYTxxL CCCccC 10.1 0.4 33.0 16.312844 1.6032e−12 1.00000 B 0.306061 0.010921 CLGxxC ECCccC 6.5 0.1 10.0 28.012557 2.3569e−12 1.00000 B 0.650000 0.005325 SGVxxS CCCchH 13.3 0.9 37.9 12.867366 3.0001e−12 1.00000 B 0.350923 0.024946 GYSxxN CEChhH 13.0 0.9 42.3 12.842946 3.1635e−12 1.00000 B 0.307329 0.021422 LDNxxK CCCccH 7.3 0.1 11.5 20.759587 4.9463e−12 1.00000 B 0.634783 0.010510 RIVxxT EECccC 8.8 0.2 24.1 18.473092 6.3694e−12 1.00000 B 0.365145 0.009037 DAAxxT CCCchH 9.0 0.3 18.0 15.524576 7.1271e−12 1.00000 B 0.500000 0.017686 GTGxxF CCChhH 8.0 0.2 12.8 16.646189 8.2070e−12 1.00000 B 0.625000 0.017357 LGNxxR CCCccH 5.5 0.0 10.3 33.262540 1.9184e−11 1.00000 B 0.533981 0.002635 HLCxxH CCCchH 9.8 0.5 14.2 13.568130 2.9460e−11 1.00000 B 0.690141 0.034352 NQTxxR HHChhH 12.9 1.0 46.4 12.053151 3.2314e−11 1.00000 B 0.278017 0.021481 IVNxxP ECCccC 10.3 0.6 22.0 13.083925 4.5307e−11 1.00000 B 0.468182 0.025815 SPGxxR CCCceE 8.0 0.3 14.9 14.892055 7.0207e−11 1.00000 B 0.536913 0.018402 QGSxxT CCCchH 6.2 0.1 11.9 20.206649 1.4310e−10 1.00000 B 0.521008 0.007738 MELxxL EECccC 7.0 0.2 10.1 14.733553 2.7272e−10 1.00000 B 0.686275 0.021233 NVGxxS CCChhH 8.5 0.4 12.5 13.078561 3.7104e−10 1.00000 B 0.680000 0.031719 ENDxxG CCChhH 8.6 0.4 12.7 13.047740 3.9246e−10 1.00000 B 0.677165 0.032073 GIPxxQ CCChhH 17.9 2.9 69.3 8.960881 6.8872e−10 1.00000 B 0.258297 0.042109 KTTxxY HHHhhH 10.0 0.7 37.4 11.632848 7.0627e−10 1.00000 B 0.267380 0.017557 FPExxT HHHhhH 14.2 1.7 58.9 9.754512 8.2132e−10 1.00000 B 0.241087 0.028739 TGDxxG ECCccC 7.1 0.2 30.0 14.821104 1.6564e−09 1.00000 B 0.236667 0.007241 DACxxD ECCccC 4.1 0.0 61.8 33.257720 1.7419e−09 1.00000 B 0.066343 0.000244 GISxxT CCChhH 10.1 0.8 21.8 10.488750 2.0178e−09 1.00000 B 0.442982 0.035657 NMDxxE CCChhH 12.4 1.4 28.5 9.575028 2.1163e−09 1.00000 B 0.435088 0.048771 TQSxxS EEEccE 21.5 6.4 177.4 6.065732 2.2502e−09 1.00000 N 0.121195 0.036167 GLSxxI EEEccC 3.0 0.0 5.0 53.996155 2.3408e−09 1.00000 B 0.600000 0.000616 SESxxH CCHhhH 3.5 0.0 5.0 50.186716 4.5726e−09 1.00000 B 0.700000 0.000971 GHGxxT CCChhH 6.0 0.2 6.1 11.911470 5.0834e−09 1.00000 B 0.983607 0.039881 NVAxxN EECccC 14.3 2.1 45.9 8.718869 5.9217e−09 1.00000 B 0.311547 0.044938 ACQxxS CCCccC 6.0 0.1 28.6 15.550736 6.0423e−09 1.00000 B 0.209790 0.004986 PSGxxK CCCccH 8.5 0.5 28.6 11.946646 6.5585e−09 1.00000 B 0.297203 0.016094 GQGxxS CCChhH 7.0 0.3 11.0 11.597337 8.0172e−09 1.00000 B 0.636364 0.030935 DGGxxK CCCccH 9.0 0.6 37.0 10.714724 8.6960e−09 1.00000 B 0.243243 0.016807 FQLxxE CCCchH 6.9 0.2 21.0 14.135162 8.7273e−09 1.00000 B 0.328571 0.010733 TGDxxC CCChhH 5.0 0.1 12.5 17.750741 8.8848e−09 1.00000 B 0.400000 0.006191 NSGxxT CCChhH 6.5 0.2 10.0 13.493999 1.1601e−08 1.00000 B 0.650000 0.022140 HHMxxP EEEecC 4.4 0.0 8.9 24.318590 1.2380e−08 1.00000 B 0.494382 0.003638 EFDxxD EEChhH 5.4 0.1 18.0 18.084978 1.2762e−08 1.00000 B 0.300000 0.004819 SCKxxT CCCeeE 11.1 1.2 35.0 9.075284 1.6971e−08 1.00000 B 0.317143 0.035046 FSTxxR CHHhhH 9.5 0.9 16.7 9.595533 1.7168e−08 1.00000 B 0.568862 0.051223 RETxxS EECccC 11.3 1.2 48.0 9.214567 2.0687e−08 1.00000 B 0.235417 0.025551 QGQxxG CCCchH 5.5 0.1 5.2 13.445268 2.0902e−08 1.00000 B 1.057692 0.027961 VTCxxG ECCccC 7.2 0.4 13.5 11.251571 2.2708e−08 1.00000 B 0.533333 0.028014 PNRxxR HHHhhH 12.2 1.5 48.9 8.713379 2.4346e−08 1.00000 B 0.249489 0.031581 KNVxxK EEEccC 13.7 2.1 42.0 8.219845 2.9154e−08 1.00000 B 0.326190 0.049934 KELxxY HHHccC 6.5 0.3 7.9 11.718695 2.9653e−08 1.00000 B 0.822785 0.036891 KCKxxH HCCccC 5.0 0.1 6.1 13.620436 3.0526e−08 1.00000 B 0.819672 0.021411 IYRxxL EECceE 3.0 0.0 4.0 33.544899 3.1613e−08 1.00000 B 0.750000 0.001993 STVxxT EEEeeE 11.4 1.4 30.4 8.710677 3.1635e−08 1.00000 B 0.375000 0.045559 SAAxxR CHHhhH 17.5 3.5 71.0 7.613866 3.2381e−08 1.00000 B 0.246479 0.049841 GFSxxD CCChhH 10.6 1.1 34.6 9.262979 3.3221e−08 1.00000 B 0.306358 0.031463 QPGxxQ CCHhhH 5.5 0.1 6.9 14.348240 3.4235e−08 1.00000 B 0.797101 0.020633 EYAxxG CCCccC 8.2 0.6 21.4 10.124027 4.2668e−08 1.00000 B 0.383178 0.027198 QHFxxL EEEecE 6.7 0.2 5.8 12.664366 4.4726e−08 1.00000 B 1.155172 0.034901 PNGxxK CCCccH 7.0 0.4 21.1 11.085149 4.4894e−08 1.00000 B 0.331754 0.017280 PTExxL CCHhhH 11.2 1.3 78.3 8.925828 4.6189e−08 1.00000 B 0.143040 0.016096 PSSxxA CCEeeE 14.1 2.2 99.1 8.057665 4.7806e−08 1.00000 B 0.142281 0.022428

TABLE 33 In Expected In P-Value P-Value Observed Null Sequence Structure Epitopes in Epi PDB Z-Score Upper Lower Distribution Ratio Probability STKxDK CEEeEE 55.6 8.7 226.6 16.255923 1.6857e−58 1.00000 N 0.245366 0.038248 TKVxKK EEEeEE 65.1 13.0 336.5 14.736016 1.5202e−48 1.00000 N 0.193462 0.038638 SAGxGR CCCcHH 13.2 0.0 46.1 75.771959 3.4177e−31 1.00000 B 0.286334 0.000656 SSTxVD HCEeEE 39.7 8.3 215.6 11.142764 2.7999e−28 1.00000 N 0.184137 0.038369 CSAxIG CCCcCC 8.5 0.0 11.9 146.471121 9.1438e−27 1.00000 B 0.714286 0.000283 TQTxKT CCCcHH 15.3 0.2 14.3 31.603282 2.1665e−26 1.00000 B 1.069930 0.014116 GSGxST CCChHH 17.9 0.4 44.9 28.229499 7.9074e−25 1.00000 B 0.398664 0.008645 NTKxDK CEEeEE 28.8 5.3 135.4 10.419284 1.0158e−24 1.00000 N 0.212703 0.039113 VACxNG ECCcCC 21.6 1.0 44.0 21.151067 8.7514e−24 1.00000 B 0.490909 0.022104 YASxRT HHCcCC 17.3 0.7 30.0 20.226529 9.0033e−21 1.00000 B 0.576667 0.023008 CSAxVG CCCcCH 6.8 0.0 16.0 121.887300 8.6362e−20 1.00000 B 0.425000 0.000194 TGTxKT CCCcHH 12.0 0.2 20.8 25.525015 3.4833e−19 1.00000 B 0.576923 0.010355 SAGxGR CCCcCH 8.5 0.0 21.6 52.240844 6.4657e−19 1.00000 B 0.393519 0.001220 NAGxTT CCChHH 9.3 0.1 13.9 31.221526 1.9447e−17 1.00000 B 0.669065 0.006303 PTWxIG CEEcCC 12.3 0.1 9.3 25.790761 2.7631e−17 1.00000 B 1.322581 0.013789 HIAxVA EEEeCC 3.0 0.0 1.0 5.254133 1.0714e−16 1.00000 B 3.000000 0.034958 DASxNT CCEhHH 1.0 0.0 1.0 6.224344 1.0823e−16 1.00000 B 1.000000 0.025162 GTMxPV CCCcCE 1.7 0.0 1.0 6.428880 1.0840e−16 1.00000 B 1.700000 0.023624 GPExSF CHHhCC 1.0 0.0 1.0 7.872524 1.0926e−16 1.00000 B 1.000000 0.015879 GYRxNG CCEeEE 1.0 0.0 1.0 18.626022 1.1070e−16 1.00000 B 1.000000 0.002874 DNAxKT CCCcHH 9.3 0.1 13.1 27.283943 1.5916e−16 1.00000 B 0.709924 0.008729 CLGxIC ECCcCC 6.0 0.0 9.0 53.549510 6.0640e−16 1.00000 B 0.666667 0.001391 LDNxGK CCCcCH 7.3 0.0 11.5 38.694812 9.3203e−16 1.00000 B 0.634783 0.003074 AAGxTT CCChHH 9.0 0.1 18.0 25.941783 1.0307e−15 1.00000 B 0.500000 0.006556 SWGxGC EECcCC 15.3 0.7 129.4 17.090125 1.1583e−15 1.00000 B 0.118238 0.005648 GVGxSA CCChHH 12.4 0.4 45.9 19.796606 1.4383e−15 1.00000 B 0.270153 0.008108 DAAxKT CCCcHH 9.0 0.2 18.0 22.774382 1.0039e−14 1.00000 B 0.500000 0.008457 IVNxTP ECCcCC 9.3 0.2 22.0 22.913053 1.8558e−14 1.00000 B 0.422727 0.007285 PGHxAL CCHhHC 9.9 0.2 12.9 19.649495 2.1377e−14 1.00000 B 0.767442 0.019076 LGNxCR CCCcCH 5.5 0.0 10.3 63.590565 3.0404e−14 1.00000 B 0.533981 0.000725 ACNxDS CCCcCC 5.0 0.0 6.0 51.992620 5.1575e−14 1.00000 B 0.833333 0.001538 CSAxIG CCCcCH 4.8 0.0 9.7 99.533355 1.1954e−13 1.00000 B 0.494845 0.000240 SGVxKS CCCcHH 11.3 0.4 32.3 16.917556 1.4040e−13 1.00000 B 0.349845 0.012975 GTGxTF CCChHH 8.0 0.2 9.8 19.427452 2.1554e−13 1.00000 B 0.816327 0.016880 QTGxGK CCCcCH 11.5 0.5 36.8 16.466361 3.1892e−13 1.00000 B 0.312500 0.012378 DGGxGK CCCcCH 9.0 0.2 36.0 19.638787 4.4953e−13 1.00000 B 0.250000 0.005607 QGSxKT CCCcHH 6.2 0.0 11.9 32.654707 5.0082e−13 1.00000 B 0.521008 0.003004 GSGxTT CCChHH 11.2 0.5 31.1 15.166466 1.1005e−12 1.00000 B 0.360129 0.016252 GAGxTT CCChHH 9.0 0.3 16.9 17.041702 1.2312e−12 1.00000 B 0.532544 0.015789 GVGxSS CCChHH 8.0 0.2 18.0 19.581495 1.7118e−12 1.00000 B 0.444444 0.008983 QSPxSL EECcEE 25.0 4.4 183.2 10.018045 2.8037e−12 1.00000 B 0.136463 0.023753 SSTxNT CCCcHH 7.0 0.1 6.0 21.807312 3.7412e−12 1.00000 B 1.166667 0.012460 RIVxYT EECcCC 8.8 0.2 23.1 18.925367 4.1481e−12 1.00000 B 0.380952 0.009004 PSGxGK CCCcCH 8.0 0.2 28.7 19.269802 4.4409e−12 1.00000 B 0.278746 0.005792 PNGxGK CCCcCH 7.0 0.1 21.1 21.242037 9.0973e−12 1.00000 B 0.331754 0.005017 KNVxCK EEEcCC 13.7 1.1 42.0 12.273416 9.7008e−12 1.00000 B 0.326190 0.025822 GAGxTS CCChHH 4.6 0.0 6.0 55.188706 1.0692e−11 1.00000 B 0.766667 0.001156 AKRxNF CCCcCE 7.3 0.1 18.3 20.637253 1.3947e−11 1.00000 B 0.398907 0.006655 NQTxNR HHChHH 12.8 0.9 46.4 12.691651 1.5524e−11 1.00000 B 0.275862 0.019330 VSWxRG EEEcCC 4.3 0.0 5.3 50.560978 1.7337e−11 1.00000 B 0.811321 0.001362 GLGxSI ECCeEE 5.5 0.0 6.2 29.505444 2.1111e−11 1.00000 B 0.887097 0.005565 ATNxRV CCChHH 8.3 0.1 6.4 20.022828 2.1648e−11 1.00000 B 1.296875 0.015713 FPExLT HHHhHH 14.2 1.3 57.9 11.378309 2.9795e−11 1.00000 B 0.245250 0.022670 GVGxSN CCChHH 6.3 0.1 12.0 21.969649 5.7852e−11 1.00000 B 0.525000 0.006723 MELxTL EECcCC 7.0 0.2 9.1 15.541949 8.4461e−11 1.00000 B 0.769231 0.021525 LGFxIV CCEeEE 4.3 0.0 7.8 38.805376 2.5905e−10 1.00000 B 0.551282 0.001568 GQGxMS CCChHH 5.0 0.1 5.0 19.958451 2.9275e−10 1.00000 B 1.000000 0.012396 QGQxIM CCCcHH 4.8 0.0 5.0 29.497827 7.6876e−10 1.00000 B 0.960000 0.005266 LNVxMV CEEeEE 3.3 0.0 5.0 64.224084 1.0266e−09 1.00000 B 0.660000 0.000527 DACxGD ECCcCC 4.1 0.0 61.8 35.388383 1.0648e−09 1.00000 B 0.066343 0.000216 NVAxKN EECcCC 13.3 1.5 43.0 9.703826 1.3782e−09 1.00000 B 0.309302 0.035495 GLSxLI EEEcCC 3.0 0.0 3.0 50.949375 1.5382e−09 1.00000 B 1.000000 0.001154 TVAxNE CHHhHH 7.8 0.4 10.6 12.570650 2.3379e−09 1.00000 B 0.735849 0.034194 QCGxCW CCEcHH 4.2 0.0 9.5 29.808739 2.4093e−09 1.00000 B 0.442105 0.002074 WGHxYA CCCcHH 5.0 0.0 4.0 23.565216 2.6158e−09 1.00000 B 1.250000 0.007152 WKNxFT HHHcCC 5.9 0.1 8.6 17.818038 2.8442e−09 1.00000 B 0.686047 0.012446 DSGxGK CCCcCH 8.3 0.4 37.5 12.773489 3.0722e−09 1.00000 B 0.221333 0.010339 NSGxTT CCChHH 6.5 0.2 9.0 14.802534 3.1087e−09 1.00000 B 0.722222 0.020643 GGTxKT CCCcHH 8.0 0.4 31.0 12.341190 3.4938e−09 1.00000 B 0.258065 0.012435 QCGxCW CCCcHH 4.8 0.0 20.2 27.916343 4.4457e−09 1.00000 B 0.237624 0.001448 VEFxFP CCCcCC 8.6 0.5 14.0 11.124863 5.3705e−09 1.00000 B 0.614286 0.038960 GSTxEK CEEeEE 10.5 0.9 24.4 10.039871 5.6240e−09 1.00000 B 0.430328 0.038632 KCKxCH HCCcCC 5.0 0.1 5.6 15.673528 5.6390e−09 1.00000 B 0.892857 0.017772 EFTxPD CCCcCC 8.6 0.6 14.0 11.007189 6.2511e−09 1.00000 B 0.614286 0.039724 GGVxKS CCCcHH 9.1 0.6 54.0 11.185057 6.4450e−09 1.00000 B 0.168519 0.010848 YGFxLH CCEeEE 4.0 0.0 4.0 20.720564 7.2597e−09 1.00000 B 1.000000 0.009231 GVGxTS CCChHH 6.0 0.2 21.1 14.676187 9.5090e−09 1.00000 B 0.284360 0.007563 YTPxLP CCCcCC 8.0 0.5 27.6 11.206864 1.2161e−08 1.00000 B 0.289855 0.016678 VDHxKT CCCcHH 6.5 0.2 27.3 14.707293 1.4173e−08 1.00000 B 0.238095 0.006798 QRRxLG CCCcHH 5.0 0.1 6.0 14.558979 1.5132e−08 1.00000 B 0.833333 0.019131 GISxET CCChHH 7.6 0.4 14.2 11.660873 1.6894e−08 1.00000 B 0.535211 0.027667 DHGxTT CCChHH 6.0 0.2 28.3 14.184164 1.6909e−08 1.00000 B 0.212014 0.006006 SGSxKS CCCcHH 6.7 0.2 20.8 13.652759 2.3784e−08 1.00000 B 0.322115 0.010926 HHMxLP EEEeCC 3.4 0.0 8.9 40.330625 2.4388e−08 1.00000 B 0.382022 0.000796 INGxSA HHCcHH 5.0 0.2 5.0 12.702857 2.4523e−08 1.00000 B 1.000000 0.030055 AGTxKS CCCcHH 4.0 0.0 5.5 19.813123 2.5620e−08 1.00000 B 0.727273 0.007316 ELGxLR CCCcCE 5.7 0.2 6.5 14.233671 2.7098e−08 1.00000 B 0.876923 0.023916 TWNxGE EECcCE 5.5 0.2 5.5 13.561891 2.7523e−08 1.00000 B 1.000000 0.029035 GLTxWK EECcCC 5.2 0.1 9.4 15.432176 2.8452e−08 1.00000 B 0.553191 0.011710 PLRxFK CCEeEE 5.4 0.2 5.7 13.543717 3.2325e−08 1.00000 B 0.947368 0.027051 ALDxPD CCCcCC 5.5 0.2 6.0 13.792962 3.3034e−08 1.00000 B 0.916667 0.025696 RVExTF CCCcCC 6.9 0.4 9.0 11.165987 3.4462e−08 1.00000 B 0.766667 0.039724 THCxVH CCEeEE 5.0 0.0 3.0 29.548453 4.0150e−08 1.00000 B 1.666667 0.003424 GSGxGT CCChHH 6.0 0.2 11.8 12.122485 4.1308e−08 1.00000 B 0.508475 0.019576 LGPxRS CCCcEE 5.7 0.2 6.0 13.118801 4.6152e−08 1.00000 B 0.950000 0.030406 AAGxST CCChHH 4.1 0.0 6.0 18.903444 4.7469e−08 1.00000 B 0.683333 0.007724 TLKxET CCEeEE 6.0 0.3 9.0 11.359947 4.8191e−08 1.00000 B 0.666667 0.029193 PGSxKG CCCcHH 5.0 0.1 10.1 14.377506 5.2693e−08 1.00000 B 0.495050 0.011555 IYRxRL EECcEE 3.0 0.0 4.0 29.281320 7.1208e−08 1.00000 B 0.750000 0.002613

TABLE 34 In Expected In P-Value P-Value Observed Null Sequence Structure Epitopes in Epi PDB Z-Score Upper Lower Distribution Ratio Probability STKVxK CEEEeE 58.5 9.1 226.5 16.684990 1.4066e−61 1.00000 N 0.258278 0.040286 GSGKxT CCCHhH 34.1 0.7 84.7 39.230822 1.9681e−47 1.00000 B 0.402597 0.008617 TKVDxK EEEEeE 65.5 14.0 338.5 14.091535 1.4697e−44 1.00000 N 0.193501 0.041227 VACKxG ECCCcC 31.1 1.2 45.0 27.213170 4.3643e−38 1.00000 B 0.691111 0.027516 TQTGxT CCCChH 18.0 0.3 17.0 33.601240 8.1511e−32 1.00000 B 1.058824 0.014834 CSAGxG CCCCcH 10.3 0.0 33.2 101.706126 5.3781e−28 1.00000 B 0.310241 0.000308 SSTKxD HCEEeE 37.9 8.0 196.6 10.787374 1.3832e−26 1.00000 N 0.192777 0.040721 AAGKxT CCCHhH 13.1 0.1 24.0 44.361614 3.6765e−26 1.00000 B 0.545833 0.003599 NTKVxK CEEEeE 29.8 5.6 135.4 10.438853 7.8103e−25 1.00000 N 0.220089 0.041391 GVGKxS CCCHhH 14.0 0.1 38.0 36.367233 1.3150e−24 1.00000 B 0.368421 0.003834 FPGHxA CCCHhH 10.6 0.1 13.0 38.749603 4.1480e−21 1.00000 B 0.815385 0.005708 GAGKxT CCCHhH 17.7 0.6 56.1 22.055939 8.2545e−21 1.00000 B 0.315508 0.010823 YASGxT HHCCcC 17.3 0.7 30.0 19.794775 1.7769e−20 1.00000 B 0.576667 0.023963 GVGKxA CCCHhH 13.4 0.2 49.1 27.315326 8.8595e−20 1.00000 B 0.272912 0.004755 SAGIxR CCCCcH 7.5 0.0 14.7 72.680577 2.7529e−19 1.00000 B 0.510204 0.000723 PTWNxG CEECcC 13.5 0.1 10.5 27.663655 3.7910e−19 1.00000 B 1.285714 0.013535 DNAGxT CCCChH 9.3 0.1 12.9 37.638562 4.8746e−19 1.00000 B 0.720930 0.004693 CSAGxG CCCCcC 7.3 0.0 18.9 67.922555 1.0491e−18 1.00000 B 0.386243 0.000610 SAGVxR CCCChH 7.3 0.0 18.1 64.671021 1.9499e−18 1.00000 B 0.403315 0.000702 VSWGxG EEECcC 13.7 0.3 111.4 24.500612 3.0198e−18 1.00000 B 0.122980 0.002692 NAGKxT CCCHhH 9.3 0.1 15.7 34.798487 4.6527e−18 1.00000 B 0.592357 0.004501 GLGFxI ECCEeE 7.2 0.0 7.9 39.857265 1.0617e−16 1.00000 B 0.911392 0.004110 TGGAxI CCCCcE 1.0 0.0 1.0 5.112750 1.0693e−16 1.00000 B 1.000000 0.036846 RYTQxN CCCCcC 1.0 0.0 1.0 5.439401 1.0739e−16 1.00000 B 1.000000 0.032694 SLPTxD CCCChH 1.0 0.0 1.0 5.557401 1.0754e−16 1.00000 B 1.000000 0.031363 ALASxA CCCCcC 1.0 0.0 1.0 5.760690 1.0777e−16 1.00000 B 1.000000 0.029252 FHISxI HCCCcE 1.8 0.0 1.0 6.089482 1.0811e−16 1.00000 B 1.800000 0.026259 ADKLxP EECCcC 1.7 0.0 1.0 6.188020 1.0820e−16 1.00000 B 1.700000 0.025451 LSERxT CCHHhH 1.0 0.0 1.0 6.443344 1.0841e−16 1.00000 B 1.000000 0.023520 ELTSxE HHHHhH 1.0 0.0 1.0 7.149093 1.0889e−16 1.00000 B 1.000000 0.019190 YIKIxA EECCcC 1.5 0.0 1.0 7.853465 1.0925e−16 1.00000 B 1.500000 0.015955 KSSTxE ECCCcC 1.0 0.0 1.0 8.919297 1.0964e−16 1.00000 B 1.000000 0.012414 RSLFxE CCCHhH 1.0 0.0 1.0 9.393303 1.0978e−16 1.00000 B 1.000000 0.011206 DAAGxT CCCChH 9.0 0.1 18.0 27.238045 4.3773e−16 1.00000 B 0.500000 0.005957 TGTGxT CCCChH 12.0 0.4 20.8 18.661705 4.5887e−16 1.00000 B 0.576923 0.018954 CKNGxT CCCCcC 16.8 1.1 47.2 15.534036 7.2121e−16 1.00000 B 0.355932 0.022272 GTGKxF CCCHhH 8.0 0.1 9.8 27.402240 9.8161e−16 1.00000 B 0.816327 0.008589 ACNGxS CCCCcC 7.0 0.0 6.0 40.200001 2.5618e−15 1.00000 B 1.166667 0.003699 CLGNxC ECCCcC 6.5 0.0 10.0 48.070386 3.8149e−15 1.00000 B 0.650000 0.001821 MELCxL EECCcC 7.0 0.1 9.1 29.548559 1.2860e−14 1.00000 B 0.769231 0.006107 SAGIxR CCCChH 5.9 0.0 20.0 61.175162 3.3437e−14 1.00000 B 0.295000 0.000464 QTGTxK CCCCcH 7.5 0.1 10.0 28.782865 3.6338e−14 1.00000 B 0.750000 0.006714 NVACxN EECCcC 14.3 1.0 43.1 13.792835 2.2413e−13 1.00000 B 0.331787 0.022206 GVGKxN CCCHhH 6.3 0.0 12.0 34.262479 3.0452e−13 1.00000 B 0.525000 0.002795 GQGIxS CCCHhH 7.0 0.1 7.0 20.184497 3.9232e−13 1.00000 B 1.000000 0.016891 NWGRxV CHHHhH 7.3 0.1 21.0 26.457581 5.7051e−13 1.00000 B 0.347619 0.003564 SGVGxS CCCChH 11.3 0.5 32.4 15.771006 5.7870e−13 1.00000 B 0.348765 0.014751 TQSPxS EEECcE 21.5 5.1 177.4 7.328957 6.0144e−13 1.00000 N 0.121195 0.028944 LDNAxK CCCCcH 6.3 0.0 10.5 31.123363 7.2899e−13 1.00000 B 0.600000 0.003867 RIVNxT EECCcC 8.8 0.2 22.1 20.487107 1.1508e−12 1.00000 B 0.398190 0.008079 DGGTxK CCCCcH 8.0 0.2 29.0 20.047467 2.4564e−12 1.00000 B 0.275862 0.005310 SSTGxT CCCChH 7.0 0.1 6.0 21.834595 3.6862e−12 1.00000 B 1.166667 0.012429 NVGKxS CCCHhH 7.5 0.1 10.0 20.522046 3.7863e−12 1.00000 B 0.750000 0.013066 NYTPxL CCCCcC 10.1 0.4 32.0 15.306066 4.9076e−12 1.00000 B 0.315625 0.012696 LGNIxR CCCCcH 4.0 0.0 7.8 60.798179 5.7878e−12 1.00000 B 0.512821 0.000554 IVNYxP ECCCcC 10.3 0.5 22.0 13.766180 1.8207e−11 1.00000 B 0.468182 0.023508 NQTPxR HHCHhH 12.9 1.0 46.4 12.190145 2.5665e−11 1.00000 B 0.278017 0.021060 NSGKxT CCCHhH 6.5 0.1 9.0 21.356062 4.3860e−11 1.00000 B 0.722222 0.010109 EYAPxG CCCCcC 8.2 0.3 12.3 14.874800 4.6252e−11 1.00000 B 0.666667 0.023547 FTVAxN CCHHhH 7.8 0.2 10.6 16.868395 4.6779e−11 1.00000 B 0.735849 0.019497 GTGKxT CCCHhH 9.0 0.3 53.3 15.122265 4.9805e−11 1.00000 B 0.168856 0.006205 EFTFxD CCCCcC 9.7 0.6 14.0 12.314175 1.6790e−10 1.00000 B 0.692857 0.040915 GGTGxT CCCChH 8.0 0.3 31.9 14.944327 2.2386e−10 1.00000 B 0.250784 0.008459 QGSGxT CCCChH 6.2 0.1 12.0 18.460914 4.1542e−10 1.00000 B 0.516667 0.009153 DSGVxK CCCCcH 8.3 0.3 31.5 14.606079 4.2534e−10 1.00000 B 0.233803 0.008518 STVExT EEEEeE 11.4 1.0 24.4 10.715271 5.4506e−10 1.00000 B 0.467213 0.040350 VDHGxT CCCChH 6.5 0.1 27.3 19.290750 6.4666e−10 1.00000 B 0.238095 0.004035 SWGRxC EECCcC 4.3 0.0 5.3 31.479143 7.5680e−10 1.00000 B 0.811321 0.003503 LSGAxK CCCCcH 4.0 0.0 4.9 29.310363 8.9269e−10 1.00000 B 0.816327 0.003780 KDYRxE CCCCcC 8.8 0.5 15.5 12.425669 1.0646e−09 1.00000 B 0.567742 0.029933 KNVAxK EEECcC 13.7 1.6 42.0 9.724955 1.2122e−09 1.00000 B 0.326190 0.038278 SGSGxS CCCChH 6.7 0.1 19.8 17.619560 1.2663e−09 1.00000 B 0.338384 0.007051 PNGSxK CCCCcH 5.0 0.1 10.1 19.647202 2.5756e−09 1.00000 B 0.495050 0.006290 EEGGxW CCCCcE 5.5 0.1 9.0 19.744546 2.6631e−09 1.00000 B 0.611111 0.008456 KCKAxH HCCCcC 5.0 0.1 5.1 16.064817 2.7922e−09 1.00000 B 0.980392 0.018626 NVGKxT CCCHhH 6.0 0.1 18.0 15.931018 3.2649e−09 1.00000 B 0.333333 0.007583 LNVGxV CEEEeE 3.3 0.0 7.7 51.472587 5.1796e−09 1.00000 B 0.428571 0.000533 GAGKxS CCCHhH 4.6 0.0 10.0 26.804049 6.0243e−09 1.00000 B 0.460000 0.002916 DKEGxF HHHCcC 14.5 2.1 53.1 8.707830 7.6359e−09 1.00000 B 0.273070 0.039712 TVAQxE CHHHhH 8.3 0.5 21.0 11.382891 8.6178e−09 1.00000 B 0.395238 0.022987 VEFTxP CCCCcC 8.6 0.6 14.0 10.667799 9.7558e−09 1.00000 B 0.614286 0.042052 GHGYxT CCCHhH 6.0 0.1 5.1 14.266534 9.7778e−09 1.00000 B 1.176471 0.024445 GSTVxK CEEEeE 10.5 1.0 24.4 9.702377 9.8438e−09 1.00000 B 0.430328 0.040973 SCKQxT CCCEeE 10.1 0.9 32.0 9.840061 1.0197e−08 1.00000 B 0.315625 0.028110 RETGxS EECCcC 11.3 1.2 48.0 9.552671 1.1284e−08 1.00000 B 0.235417 0.024074 NGSGxS CCCChH 5.0 0.1 13.1 17.153749 1.2945e−08 1.00000 B 0.381679 0.006313 HHMExP EEEEcC 4.4 0.0 8.9 23.470902 1.6376e−08 1.00000 B 0.494382 0.003902 DHGKxT CCCHhH 6.0 0.2 31.9 14.277130 1.6708e−08 1.00000 B 0.188088 0.005259 SPGAxR CCCCeE 6.0 0.2 10.9 12.858950 1.8510e−08 1.00000 B 0.550459 0.018981 ACIAxE CCCCcC 6.3 0.3 7.0 11.516135 2.1334e−08 1.00000 B 0.900000 0.040631 ELGPxR CCCCcE 5.7 0.2 6.0 14.099971 2.2990e−08 1.00000 B 0.950000 0.026441 QHFKxL EEEEcE 6.7 0.2 5.8 13.135377 3.1489e−08 1.00000 B 1.155172 0.032522 DLEAxG EEEEcC 2.2 0.0 4.0 119.847863 3.4045e−08 1.00000 B 0.550000 0.000084 RSFKxF EEEEeE 5.4 0.2 5.7 13.424145 3.5216e−08 1.00000 B 0.947368 0.027520 SVGKxS CCCHhH 4.0 0.0 13.0 21.268702 3.6221e−08 1.00000 B 0.307692 0.002681 IYRDxL EECCeE 3.0 0.0 4.0 32.585874 3.7597e−08 1.00000 B 0.750000 0.002112 PNVGxS CCCChH 6.0 0.2 19.4 12.859611 3.8924e−08 1.00000 B 0.309278 0.010579 GTGKxC CCCHhH 4.0 0.0 6.1 18.981083 4.3099e−08 1.00000 B 0.655738 0.007173 GPLRxF CCCEeE 5.5 0.2 5.8 13.124718 4.6797e−08 1.00000 B 0.948276 0.029294

TABLE 35 In Expected In P-Value P-Value Observed Null Sequence Structure Epitopes in Epi PDB Z-Score Upper Lower Distribution Ratio Probability STKVDK CEEEEE 54.6 7.3 226.6 17.814795 7.7075e−70 1.00000 N 0.240953 0.032161 TKVDKK EEEEEE 65.1 11.0 336.5 16.615803 3.4212e−61 1.00000 N 0.193462 0.032601 SSTKVD HCEEEE 37.4 6.3 196.6 12.532954 3.0773e−35 1.00000 N 0.190234 0.032272 GSGKST CCCHHH 17.9 0.2 43.8 38.350752 2.9572e−29 1.00000 B 0.408676 0.004880 TQTGKT CCCCHH 15.3 0.2 14.3 32.174467 1.3214e−26 1.00000 B 1.069930 0.013626 SAGIGR CCCCCH 7.5 0.0 14.7 117.545793 3.3253e−22 1.00000 B 0.510204 0.000277 VACKNG ECCCCC 20.6 1.0 43.0 19.828434 5.1410e−22 1.00000 B 0.479070 0.023263 YASGRT HHCCCC 17.3 0.6 30.0 22.109277 5.3354e−22 1.00000 B 0.576667 0.019434 SAGVGR CCCCHH 7.3 0.0 18.1 109.112108 1.3092e−21 1.00000 B 0.403315 0.000247 DNAGKT CCCCHH 9.3 0.0 12.9 47.146776 8.7394e−21 1.00000 B 0.720930 0.003000 NAGKTT CCCHHH 9.3 0.0 13.9 46.853654 1.4104e−20 1.00000 B 0.669065 0.002819 CSAGIG CCCCCC 6.3 0.0 11.9 123.156446 6.8159e−20 1.00000 B 0.529412 0.000220 GVGKSA CCCHHH 12.4 0.2 44.0 28.043320 4.8288e−19 1.00000 B 0.281818 0.004327 TGTGKT CCCCHH 12.0 0.2 19.8 24.719102 5.6749e−19 1.00000 B 0.606061 0.011586 AAGKTT CCCHHH 9.0 0.1 18.0 37.604373 1.4562e−18 1.00000 B 0.500000 0.003152 DAAGKT CCCCHH 9.0 0.1 18.0 35.241267 4.6128e−18 1.00000 B 0.500000 0.003584 CLGNIC ECCCCC 6.0 0.0 9.0 78.058006 6.6601e−18 1.00000 B 0.666667 0.000656 GTDVVG CCCHHH 2.0 0.0 2.0 11.083550 7.0003e−18 1.00000 B 1.000000 0.016020 PTWNIG CEECCC 12.3 0.1 9.3 26.586731 1.6109e−17 1.00000 B 1.322581 0.012986 CSAGVG CCCCCH 5.8 0.0 16.0 124.248581 4.0798e−17 1.00000 B 0.362500 0.000136 HIASVA EEEECC 3.0 0.0 1.0 5.592042 1.0758e−16 1.00000 B 3.000000 0.030988 ALASTA CCCCCC 1.0 0.0 1.0 6.347379 1.0833e−16 1.00000 B 1.000000 0.024219 GTMKPV CCCCCE 1.7 0.0 1.0 6.517403 1.0847e−16 1.00000 B 1.700000 0.023001 AEKGLV HHHCCC 1.0 0.0 1.0 6.758211 1.0864e−16 1.00000 B 1.000000 0.021425 ANALAS CCCCCC 1.0 0.0 1.0 7.841519 1.0925e−16 1.00000 B 1.000000 0.016003 YIKIHA EECCCC 1.5 0.0 1.0 7.920066 1.0928e−16 1.00000 B 1.500000 0.015692 RITTLD EEEEEE 1.0 0.0 1.0 8.134587 1.0937e−16 1.00000 B 1.000000 0.014887 NALAST CCCCCC 1.0 0.0 1.0 8.915828 1.0964e−16 1.00000 B 1.000000 0.012424 RSLFLE CCCHHH 1.0 0.0 1.0 10.050382 1.0993e−16 1.00000 B 1.000000 0.009803 GYRDNG CCEEEE 1.0 0.0 1.0 18.161797 1.1069e−16 1.00000 B 1.000000 0.003023 GSGKTT CCCHHH 11.2 0.2 31.1 22.191557 4.5690e−16 1.00000 B 0.360129 0.007897 SAGIGR CCCCHH 5.9 0.0 20.0 88.105700 8.7484e−16 1.00000 B 0.295000 0.000224 DGGTGK CCCCCH 8.0 0.1 29.0 32.442436 1.3906e−15 1.00000 B 0.275862 0.002070 LDNAGK CCCCCH 6.3 0.0 10.5 52.016926 1.6033e−15 1.00000 B 0.600000 0.001392 GTGKTF CCCHHH 8.0 0.1 9.8 26.155884 2.0446e−15 1.00000 B 0.816327 0.009416 NTKVDK CEEEEE 28.8 4.5 135.4 11.725183 2.2882e−15 1.00000 B 0.212703 0.032917 SGVGKS CCCCHH 11.3 0.3 32.4 20.191824 3.7718e−15 1.00000 B 0.348765 0.009246 GAGKTT CCCHHH 9.0 0.1 16.9 23.668066 4.2461e−15 1.00000 B 0.532544 0.008359 GVGKSS CCCHHH 8.0 0.1 18.0 27.100944 1.1064e−14 1.00000 B 0.444444 0.004761 ACNGDS CCCCCC 5.0 0.0 6.0 58.063960 1.7133e−14 1.00000 B 0.833333 0.001234 IVNYTP ECCCCC 9.3 0.2 22.0 21.034466 8.1515e−14 1.00000 B 0.422727 0.008602 MELCTL EECCCC 7.0 0.1 9.1 25.425349 1.0255e−13 1.00000 B 0.769231 0.008220 CSAGIG CCCCCH 4.5 0.0 9.7 105.776723 1.0959e−13 1.00000 B 0.463918 0.000186 LGNICR CCCCCH 4.0 0.0 7.8 98.011647 1.2752e−13 1.00000 B 0.512821 0.000213 QTGTGK CCCCCH 7.5 0.1 10.0 25.450191 1.9828e−13 1.00000 B 0.750000 0.008561 GVGKSN CCCHHH 6.3 0.0 11.0 31.334402 7.4332e−13 1.00000 B 0.572727 0.003642 GQGIMS CCCHHH 5.0 0.0 5.0 36.328434 7.6590e−13 1.00000 B 1.000000 0.003774 SSTGNT CCCCHH 7.0 0.1 6.0 22.498314 2.5846e−12 1.00000 B 1.166667 0.011715 NVACKN EECCCC 13.3 0.9 43.0 12.867025 3.8275e−12 1.00000 B 0.309302 0.021930 RIVNYT EECCCC 8.8 0.2 22.1 18.891805 3.9882e−12 1.00000 B 0.398190 0.009447 DSGVGK CCCCCH 8.3 0.2 35.5 19.948620 4.0221e−12 1.00000 B 0.233803 0.004704 QGSGKT CCCCHH 6.2 0.1 12.0 27.121341 4.5823e−12 1.00000 B 0.516667 0.004301 PNGSGK CCCCCH 5.0 0.0 10.1 37.000198 5.0129e−12 1.00000 B 0.495050 0.001798 GGTGKT CCCCHH 8.0 0.2 30.9 19.161996 5.2279e−12 1.00000 B 0.258900 0.005436 KNVACK EEECCC 13.7 1.1 42.0 12.473295 6.8302e−12 1.00000 B 0.326190 0.025102 GAGKTS CCCHHH 4.6 0.0 6.0 57.795480 7.3969e−12 1.00000 B 0.766667 0.001054 NQTPNR HHCHHH 12.8 0.9 46.4 12.726660 1.4674e−11 1.00000 B 0.275862 0.019236 VDHGKT CCCCHH 6.5 0.1 27.3 25.428433 2.6010e−11 1.00000 B 0.238095 0.002352 QALSGL HHHHHH 3.0 0.0 5.0 109.114549 3.4511e−11 1.00000 B 0.600000 0.000151 VSWGRG EEECCC 4.3 0.0 5.3 44.147984 5.1163e−11 1.00000 B 0.811321 0.001785 SGSGKS CCCCHH 6.7 0.1 19.8 22.942534 5.9262e−11 1.00000 B 0.338384 0.004218 NSGKTT CCCHHH 6.5 0.1 9.0 20.353985 7.7073e−11 1.00000 B 0.722222 0.011109 GVGKTS CCCHHH 6.0 0.1 20.1 21.831417 9.5206e−11 1.00000 B 0.298507 0.003679 DHGKTT CCCHHH 6.0 0.1 28.2 20.841979 2.0824e−10 1.00000 B 0.212766 0.002868 LNVGMV CEEEEE 3.3 0.0 5.0 83.763342 2.0891e−10 1.00000 B 0.660000 0.000310 QCGSCW CCCCHH 4.4 0.0 20.2 40.547665 3.4174e−10 1.00000 B 0.217822 0.000580 PSGSGK CCCCCH 4.0 0.0 8.0 35.524057 4.3113e−10 1.00000 B 0.500000 0.001577 GGVGKS CCCCHH 9.1 0.5 53.2 12.788361 8.0126e−10 1.00000 B 0.171053 0.008654 GTGKTT CCCHHH 8.0 0.3 45.2 13.827063 9.0377e−10 1.00000 B 0.176991 0.006888 GSTVEK CEEEEE 10.5 0.8 24.4 11.145641 9.7627e−10 1.00000 B 0.430328 0.032173 LSGAGK CCCCCH 4.0 0.0 4.9 28.128509 1.2381e−09 1.00000 B 0.816327 0.004102 EFTFPD CCCCCC 8.6 0.5 14.0 12.223542 1.3797e−09 1.00000 B 0.614286 0.032760 VEFTFP CCCCCC 8.6 0.5 14.0 12.179844 1.4535e−09 1.00000 B 0.614286 0.032978 GLGFSI ECCEEE 4.0 0.0 4.4 26.233665 1.5884e−09 1.00000 B 0.909091 0.005251 NGSGKS CCCCHH 5.0 0.1 13.1 21.272338 1.6003e−09 1.00000 B 0.381679 0.004143 SWGRGC EECCCC 4.3 0.0 5.3 28.630970 1.6081e−09 1.00000 B 0.811321 0.004230 QGQGIM CCCCHH 4.8 0.0 5.0 26.582255 1.7583e−09 1.00000 B 0.960000 0.006475 KCKACH HCCCCC 5.0 0.1 5.1 16.352193 2.3466e−09 1.00000 B 0.980392 0.017989 AAGKST CCCHHH 4.1 0.0 6.0 26.934773 2.8975e−09 1.00000 B 0.683333 0.003833 NVGKST CCCHHH 6.0 0.1 18.0 15.762169 3.6864e−09 1.00000 B 0.333333 0.007740 PNVGKS CCCCHH 6.0 0.1 19.0 15.593755 4.3819e−09 1.00000 B 0.315789 0.007483 WGHGYA CCCCHH 5.0 0.0 4.0 21.902956 4.6751e−09 1.00000 B 1.250000 0.008269 GHGYAT CCCHHH 5.0 0.0 4.0 20.616189 7.5561e−09 1.00000 B 1.250000 0.009323 RVEFTF CCCCCC 6.9 0.3 9.0 12.256272 1.1956e−08 1.00000 B 0.766667 0.033331 ELGPLR CCCCCE 5.7 0.1 6.0 15.016070 1.2482e−08 1.00000 B 0.950000 0.023394 GTGKSC CCCHHH 4.0 0.0 5.1 20.988541 1.3877e−08 1.00000 B 0.784314 0.007044 STGAGK CCCCCH 4.6 0.0 7.1 23.047849 1.4152e−08 1.00000 B 0.647887 0.005546 QRRGLG CCCCHH 5.0 0.1 6.0 14.511493 1.5619e−08 1.00000 B 0.833333 0.019253 INGNSA HHCCHH 5.0 0.1 5.0 13.172405 1.7239e−08 1.00000 B 1.000000 0.028009 STVEKT EEEEEE 9.5 0.8 24.4 10.028684 1.8503e−08 1.00000 B 0.389344 0.032003 TLKGET CCEEEE 6.0 0.2 9.0 12.310119 1.9569e−08 1.00000 B 0.666667 0.025076 PLRSFK CCEEEE 5.4 0.1 5.7 13.898421 2.5175e−08 1.00000 B 0.947368 0.025727 GLTDWK EECCCC 5.2 0.1 9.4 15.570150 2.6117e−08 1.00000 B 0.553191 0.011510 PGSGKG CCCCHH 5.0 0.1 10.1 15.466402 2.6172e−08 1.00000 B 0.495050 0.010033 GPLRSF CCCEEE 5.5 0.2 5.8 13.909240 2.6726e−08 1.00000 B 0.948276 0.026176 SPSSLS ECCEEE 15.8 2.7 85.6 8.005725 2.9307e−08 1.00000 B 0.184579 0.032087 LGPLRS CCCCEE 5.7 0.2 6.0 13.596746 3.2676e−08 1.00000 B 0.950000 0.028372 PSSLSA CCEEEE 13.1 1.8 90.4 8.382019 3.8044e−08 1.00000 B 0.144912 0.020372 SVGKTS CCCHHH 4.0 0.0 10.0 20.358152 4.3082e−08 1.00000 B 0.400000 0.003802

TABLE 36 (Table 36, in its entirety, discloses SEQ ID NOS 3,187-5,226, respectively, in order of appearance) Num Num Inter- Num Non- In Ex- Null Crys- face Chain- Water Epi- pected In P-Value Observed Prob- tal Inter- sets Sol- Sequence Structure topes in Epi PDB Z-Score Upper Ratio ability Sets sets 25 vent FxGHxA CcCHhH 10.6 0.1 13 40.14033 2.0626e−21 0.815385 0.005323 11 6 1 0.021 FPGHxA CCCHhH 10.6 0.1 13 38.7496 4.1480e−21 0.815385 0.005708 11 6 1 0.021 FPxHxA CCcHhH 11.6 0.1 14.2 36.45081 4.1020e−22 0.816901 0.007059 12 6 1 0.021 ExxxMD HhhhEC 16.7 0.2 36.2 35.39318 6.7544e−27 0.461326 0.006027 17 8 1 5.181 FPGH CCCH 11.5 0.2 16.2 28.66959 1.9821e−19 0.709877 0.009756 11 6 1 0.021 FxxHxA CccHhH 11.6 0.2 19 27.92433 7.9156e−19 0.610526 0.008899 12 6 1 0.021 ERxxMD HHhhEC 15.1 0.2 36.2 30.59899 8.7736e−24 0.417127 0.00656 17 8 1 5.134 LGxSI CCeEE 12.5 0.2 38.3 25.47832 3.4342e−18 0.326371 0.006089 12 13 8 5 FxGH CcCH 12.2 0.2 23.1 25.02609 1.0525e−18 0.528139 0.010002 12 7 2 0.021 PxHxAL CcHhHC 11 0.3 13.1 20.59324 3.3394e−17 0.839695 0.021144 11 5 1 0 PGHxxL CCHhhC 11.7 0.3 13 21.21613 1.9065e−17 0.9 0.022743 11 5 1 0 RxxMDS HhhECC 16.7 0.4 42.2 24.91901 6.1180e−22 0.395735 0.010205 18 10 1 5.157 RxxMD HhhEC 17.1 0.6 44.2 22.2385 2.7644e−21 0.386878 0.012675 19 10 1 5.157 KxxFTV HhcCCH 11.1 0.4 14.1 17.68718 1.7765e−15 0.787234 0.026782 12 7 7 0 KxxFxV HhcCcH 11.6 0.4 15.8 17.89308 3.6601e−15 0.734177 0.025436 13 8 8 0 FPGxxA CCChhH 11.6 0.4 23 17.67412 2.5125e−14 0.504348 0.017749 11 6 1 0.021 NYTxxL CCCccC 10.1 0.4 33 16.31284 1.6032e−12 0.306061 0.010921 11 2 1 1.5 VACxxG ECCccC 33.4 1.2 47.1 29.57423 6.3139e−42 0.70913 0.025811 29 15 1 5.755 PxHxxL CcHhhC 12.9 0.5 18.3 18.1817 2.5192e−16 0.704918 0.026188 12 5 1 0 FPxH CCcH 12.5 0.5 22.2 17.81482 2.2978e−15 0.563063 0.020995 12 6 1 0.021 LxxNVM CchHHH 18.1 0.7 30.9 20.92111 3.8340e−22 0.585761 0.022891 18 12 1 1.542 VACKxG ECCCcC 31.1 1.2 45 27.21317 4.3643e−38 0.691111 0.027516 27 13 1 5.505 NYTPxL CCCCcC 10.1 0.4 32 15.30607 4.9076e−12 0.315625 0.012696 11 2 1 1.5 CKxGxT CCcCcC 27.2 1.1 50 25.15354 9.5225e−32 0.544 0.022017 26 14 1 5.231 VxCxxG EcCccC 40.5 1.7 79.3 30.25631 1.7042e−45 0.510719 0.021207 37 19 1 8.755 PGHxA CCHhH 11.3 0.5 18.8 15.37671 2.0088e−13 0.601064 0.026934 12 7 2 0.688 VACxNG ECCcCC 21.6 1 44 21.15107 8.7514e−24 0.490909 0.022104 19 13 1 4.438 VxCKxG EcCCcC 37.2 1.7 58.6 27.64679 3.2831e−42 0.634812 0.028979 34 16 1 8.505 MDSS ECCC 14.9 0.7 43.2 17.35742 4.1795e−16 0.344907 0.015781 15 10 2 5.204 VxCxNG EcCcCC 27.6 1.3 56.3 22.96562 2.7459e−29 0.490231 0.02379 25 15 1 7.438 VACKNG ECCCCC 20.6 1 43 19.82843 5.1410e−22 0.47907 0.023263 18 12 1 4.438 NxTPxL CcCCcC 11.8 0.6 39.8 14.91701 1.9147e−12 0.296482 0.014437 13 4 3 3.334 GFTxS CCHhH 25.7 1.3 42.2 21.82477 7.8086e−28 0.609005 0.030577 24 15 1 4.165 IVNYxP ECCCcC 10.3 0.5 22 13.76618 1.8207e−11 0.468182 0.023508 12 2 1 1.375 GFxNS CChHH 25.7 1.3 43.2 21.48449 2.0443e−27 0.594907 0.030734 24 15 1 4.171 GFTNS CCHHH 24.7 1.3 41.2 20.89447 2.9243e−26 0.599515 0.031442 23 14 1 4.165 VxCKNG EcCCCC 26.6 1.4 55.2 21.38084 4.0094e−27 0.481884 0.025784 24 14 1 7.438 IVxYxP ECcCcC 10.3 0.6 23 13.2175 4.2034e−11 0.447826 0.024211 12 2 1 1.375 IVNxxP ECCccC 10.3 0.6 22 13.08393 4.5307e−11 0.468182 0.025815 12 2 1 1.375 LxxNxM CchHhH 18.1 1 44.6 17.17364 1.8356e−18 0.40583 0.022712 18 12 1 1.542 GHxxL CHhhC 13.2 0.8 17.8 14.59737 6.8060e−15 0.741573 0.042626 12 7 2 0 LxxxVM CchhHH 23.7 1.4 59.7 19.2235 6.7876e−23 0.396985 0.023116 22 14 2 1.542 ACKxG CCCcC 34.1 2 46.4 23.18366 1.3729e−36 0.734914 0.043173 29 16 1 6.755 GxTNS CcHHH 24.7 1.5 42.7 19.6171 6.3209e−25 0.578454 0.034045 23 14 1 4.165 RIxxNL HHhhHH 16.5 1 44 15.84119 4.4922e−16 0.375 0.022308 17 5 2 5.708 NxGYH EcCCE 11.7 0.7 37.8 13.20822 2.2537e−11 0.309524 0.018678 13 7 1 4.817 VACxN ECCcC 21.9 1.3 45 18.01829 2.2608e−21 0.486667 0.029818 20 14 1 5.188 PSVY CEEE 17.5 1.1 268.7 15.82354 1.2792e−15 0.065128 0.004023 23 13 1 3.071 CxNGxT CcCCcC 19 1.2 51.6 16.57241 2.1832e−18 0.368217 0.022926 19 15 1 4.652 CKNGxT CCCCcC 16.8 1.1 47.2 15.53404 7.2121e−16 0.355932 0.022272 16 12 1 3.438 FTxxxN CChhhH 10 0.6 19.8 12.03098 1.2267e−10 0.505051 0.031658 10 6 6 1 NxQxQF CcCcCE 10.1 0.6 29.2 11.9082 3.6689e−10 0.34589 0.022079 11 11 1 1 QFxTN CEcCC 17.3 1.1 28.1 15.7038 1.4457e−17 0.615658 0.039391 13 15 1 6 NxxYH EccCE 11.7 0.8 37.8 12.74759 4.4345e−11 0.309524 0.019907 13 7 1 4.817 ERxxxD HHhheC 16.2 1 36.2 15.05407 8.6591e−16 0.447514 0.028832 18 9 1 6.134 LxxKDY HhhCCC 11.4 0.8 17.5 13.25842 4.4705e−13 0.708571 0.045827 11 5 2 0.333 QFNTN CECCC 16.8 1.1 28.1 15.36943 1.1857e−16 0.597865 0.038692 12 14 1 6 NVACK EECCC 24.2 1.6 45 18.28235 1.9905e−23 0.537778 0.035242 23 10 1 5.523 PGxxAL CChhHC 10.3 0.7 15.5 11.89251 7.8512e−11 0.664516 0.044128 10 5 1 0 VxCKN EcCCC 27.9 1.9 55.4 19.44521 3.8832e−26 0.50361 0.033503 26 16 1 8.188 NVACxN EECCcC 14.3 1 43.1 13.79284 2.2413e−13 0.331787 0.022206 14 10 1 4.392 CKNxxT CCCccC 16.8 1.2 47.7 14.76365 3.0318e−15 0.352201 0.024136 16 12 1 3.438 NxTPNR HhCHHH 13.8 1 46.4 13.28837 1.7188e−12 0.297414 0.020563 14 10 1 3.816 VAxKxG ECcCcC 31.1 2.2 50.4 20.1751 6.0519e−30 0.617063 0.042673 27 13 1 5.505 VACKN ECCCC 20.9 1.5 43 16.41255 2.2938e−19 0.486047 0.033792 19 13 1 5.188 GYSxxN CEChhH 13 0.9 42.3 12.84295 3.1635e−12 0.307329 0.021422 15 15 1 3.062 GFxxxG CEeeeE 11.7 0.8 72.6 12.12061 2.1618e−10 0.161157 0.011234 12 13 6 3.5 NQTPNR HHCHHH 12.8 0.9 46.4 12.72666 1.4674e−11 0.275862 0.019236 13 9 1 3.816 YSxMS CCcEE 11.7 0.8 42.8 12.16388 1.2625e−10 0.273364 0.019069 15 14 1 1.966 KxYRxE CcCCcC 11.8 0.8 21.3 12.33046 1.9943e−11 0.553991 0.038696 10 4 2 0.333 NxACK EeCCC 24.2 1.7 45 17.62335 9.2961e−23 0.537778 0.037658 23 10 1 5.523 NQTxNR HHChHH 12.8 0.9 46.4 12.69165 1.5524e−11 0.275862 0.01933 13 9 1 3.816 NVxCK EEcCC 24.2 1.7 45 17.59016 1.0058e−22 0.537778 0.037786 23 10 1 5.523 YTPxL CCCcC 11.1 0.8 39.8 11.76239 2.0298e−10 0.278894 0.019713 12 3 1 1.5 NVAC EECC 26.5 1.9 49.4 18.34496 1.9069e−24 0.536437 0.037918 25 12 1 5.773 NVACKN EECCCC 13.3 0.9 43 12.86703 3.8275e−12 0.309302 0.02193 13 9 1 4.392 QFNxN CECcC 17.1 1.2 28.1 14.7482 8.3663e−17 0.608541 0.043159 12 14 1 6 FTVA CCHH 13.1 0.9 19.6 12.93532 2.1141e−13 0.668367 0.047415 14 8 7 0 VxCxN EcCcC 28.9 2.1 67.3 19.01138 1.1251e−25 0.429421 0.030557 27 17 1 8.188 YSTMS CCCEE 11.7 0.8 42.8 12.01448 1.5892e−10 0.273364 0.01949 15 14 1 3.966 PPGPP CCCCC 16.8 1.2 31 14.51712 1.0146e−15 0.541935 0.038746 2 17 2 0 NxTxNR HhChHH 13.8 1 47.4 13.0352 2.7237e−12 0.291139 0.020818 14 10 1 3.816 ERxxM HHhhE 17.3 1.2 36.5 14.66555 4.8047e−16 0.473973 0.034006 18 9 1 5.134 GxGF EcCE 16.8 1.2 40.5 14.39904 3.7361e−15 0.414815 0.029841 16 18 9 7.666 NVxCxN EEcCcC 14.3 1 43.1 13.21465 6.2025e−13 0.331787 0.023961 14 10 1 4.392 YxTMS CcCEE 11.7 0.8 42.8 11.91659 1.8497e−10 0.273364 0.019773 15 14 1 3.966 GFxxS CChhH 27 2 67.8 18.15516 5.3814e−24 0.39823 0.028894 26 18 2 4.171 VACK ECCC 33.2 2.4 45 20.37365 1.4230e−32 0.737778 0.053619 30 14 1 6.435 VxCK EcCC 42 3.1 60.9 22.84323 2.8454e−40 0.689655 0.050241 40 20 1 9.435 NxAC EeCC 27 2 50.4 18.15349 6.3631e−25 0.535714 0.039237 25 12 1 5.773 NxTPxR HhCHhH 13.9 1 46.4 12.9093 2.3592e−12 0.299569 0.021942 14 10 1 3.829 SxMS CcEE 14.9 1.1 51.5 13.35327 3.9684e−13 0.28932 0.021211 17 17 1 4.466 STMS CCEE 14.9 1.1 42.8 13.37733 2.6426e−13 0.348131 0.025541 17 17 1 4.466 NVxC EEcC 26.5 1.9 52.2 17.92263 8.5115e−24 0.507663 0.037341 25 12 1 5.773 NxACxN EeCCcC 14.3 1.1 43 12.98435 9.3387e−13 0.332558 0.024775 14 10 1 4.392 QFxT CEcC 21.3 1.6 29.7 16.06162 9.1250e−21 0.717172 0.053568 17 19 2 7 TVAxxE CHHhhH 14.8 1.1 24.2 13.27204 6.4829e−14 0.61157 0.046058 15 9 8 1 NQTPxR HHCHhH 12.9 1 46.4 12.19015 2.5665e−11 0.278017 0.02106 13 9 1 3.829 TMxRI HHhHH 11.4 0.9 25.5 11.525 1.5721e−10 0.447059 0.033919 14 4 1 3.146 YxxMS CccEE 11.7 0.9 44.7 11.58861 3.2547e−10 0.261745 0.019868 15 14 1 3.966 ACxNG CCcCC 22.7 1.7 46.9 16.27224 5.2201e−20 0.484009 0.03678 20 15 2 4.549 ACKNG CCCCC 21.6 1.7 43 15.80433 3.8946e−19 0.502326 0.038517 18 13 1 4.438 KxVxCK EeEcCC 17.6 1.4 47.7 14.18337 3.3780e−15 0.368973 0.028318 19 10 1 2.55 KxVAC EeECC 17.6 1.4 42 14.19049 2.2162e−15 0.419048 0.032245 19 12 1 2.8 KNVACK EEECCC 13.7 1.1 42 12.4733 6.8302e−12 0.32619 0.025102 15 9 1 2.431 RxxMxS HhhEcC 16.7 1.3 42.2 13.80189 1.5849e−14 0.395735 0.030483 18 10 1 5.157 KxVACK EeECCC 15.3 1.2 42 13.18095 1.8560e−13 0.364286 0.028111 16 9 1 2.55 NQTxxR HHChhH 12.9 1 46.4 12.05315 3.2314e−11 0.278017 0.021481 13 9 1 3.829 KNxAC EEeCC 16.4 1.3 42 13.64298 2.3347e−14 0.390476 0.030201 18 12 1 2.681 NxTxxR HhChhH 13.9 1.1 47.4 12.49716 5.0108e−12 0.293249 0.022727 14 10 1 3.829 FxTxxR ChHhhH 13.6 1.1 20.2 12.53096 6.0951e−13 0.673267 0.052338 13 7 1 2.833 GYxxxN CEchhH 14 1.1 42.3 12.53642 1.6774e−12 0.330969 0.025738 16 16 1 3.062 NVxCKN EEcCCC 13.3 1 43 12.19847 1.2220e−11 0.309302 0.024087 13 9 1 4.392 KNVAC EEECC 15.9 1.2 42.1 13.36749 7.6225e−14 0.377672 0.029438 18 12 1 2.681 NxxCxN EecCcC 14.5 1.1 43 12.72668 1.5589e−12 0.337209 0.026349 14 11 1 4.438 KNxxC EEecC 16.4 1.3 42 13.54722 2.8206e−14 0.390476 0.030577 18 12 1 2.681 KNVxC EEEcC 15.9 1.2 42.1 13.32532 8.2636e−14 0.377672 0.029601 18 12 1 2.681 WCxP CChH 33.3 2.6 62.5 19.37311 4.2055e−29 0.5328 0.041887 35 40 17 8.539 QFNT CECC 19.8 1.6 28.2 15.03871 1.4634e−18 0.702128 0.05523 15 17 1 7 KNVxCK EEEcCC 13.7 1.1 42 12.27342 9.7008e−12 0.32619 0.025822 15 9 1 2.431 VAxKNG ECcCCC 20.6 1.6 43 15.11451 7.1138e−18 0.47907 0.038057 18 12 1 4.438 FRxxD HHhhC 17.5 1.4 102.5 13.73082 3.4864e−14 0.170732 0.013607 20 21 8 1.25 RxxLPE HhhCCC 11.6 0.9 30.6 11.27164 3.4023e−10 0.379085 0.030226 12 7 6 2.06 FTxS CHhH 27.7 2.2 52.5 17.49009 6.0171e−24 0.527619 0.042219 26 17 2 4.171 FTNS CHHH 25.7 2.1 47.2 16.82928 2.2403e−22 0.544492 0.043704 24 15 1 4.171 FxGxxA CcChhH 13.1 1.1 51 11.86862 2.5395e−11 0.256863 0.02063 13 8 3 0.021 NxACKN EeCCCC 13.3 1.1 43 11.98009 1.8020e−11 0.309302 0.024858 13 9 1 4.392 QTxxAK HHhhHH 11.5 0.9 25.1 11.04198 3.3849e−10 0.458167 0.037806 8 10 4 2 SxKPxY CcCCcC 12.3 1 23.8 11.4035 4.1050e−11 0.516807 0.042941 12 11 3 0.511 TxxLxK CccCcH 12.8 1.1 41.4 11.51471 9.3815e−11 0.309179 0.025747 15 7 6 2 VAC ECC 35.5 3 69.4 19.30368 1.0904e−29 0.511527 0.042754 32 16 1 6.685 ExxxxD HhhheC 18.8 1.6 44.9 13.98063 1.0075e−15 0.418708 0.035042 19 10 2 6.181 KNxACK EEeCCC 13.7 1.1 42 11.87452 1.9766e−11 0.32619 0.027349 15 9 1 2.431 NxxCK EecCC 24.2 2 45 15.92761 6.0120e−21 0.537778 0.045091 23 10 1 5.523 NxxxQF CcccCE 17.8 1.5 51.1 13.54533 1.1983e−14 0.346337 0.029216 15 16 2 5 FxNS ChHH 27.7 2.3 55.4 16.95863 3.7819e−23 0.5 0.042157 26 17 2 4.176 QTPNR HCHHH 17.2 1.5 46.4 13.22939 2.0671e−14 0.37069 0.031495 18 13 1 5.816 GSTVE CEEEE 15.9 1.4 24.4 12.86514 2.1829e−14 0.651639 0.055473 17 10 1 1.048 ExxxM HhhhE 21 1.8 40.6 14.696 2.8903e−18 0.517241 0.044034 20 11 2 5.181 CExxxY EEcccC 17.7 1.5 50.9 13.36287 2.0202e−14 0.347741 0.029713 18 13 1 8.785 STVExT EEEEeE 11.4 1 24.4 10.71527 5.4506e−10 0.467213 0.04035 12 4 1 1 NQxPNR HHcHHH 12.9 1.1 47.4 11.21815 1.4078e−10 0.272152 0.023798 13 9 1 3.818 MxxSRN HhhHCC 13.4 1.2 42 11.44511 4.7252e−11 0.319048 0.027951 16 6 1 1.311 QTPxR HCHhH 17.2 1.5 46.4 12.98164 3.4999e−14 0.37069 0.032542 18 13 1 5.829 QTxNR HChHH 17.2 1.5 46.4 12.93232 3.8897e−14 0.37069 0.032756 18 13 1 5.816 KNxxCK EEecCC 13.7 1.2 42 11.50467 3.8780e−11 0.32619 0.028883 15 9 1 2.431 QFxxN CEccC 17.6 1.6 32.4 13.17019 6.2448e−15 0.54321 0.048103 13 15 1 6 NxxCKN EecCCC 13.3 1.2 43 11.28729 6.3736e−11 0.309302 0.027552 13 9 1 4.392 GxTxS CcHhH 25.7 2.3 77.1 15.70055 6.1084e−20 0.333333 0.029715 24 15 1 4.165 WCGP CCHH 23.2 2.1 48.1 14.99016 3.7261e−19 0.482328 0.043149 23 26 10 4.472 GxGxxI EcCeeE 12.5 1.1 47.7 10.87978 4.3984e−10 0.262055 0.023487 15 20 10 3.741 NxxPNR HhcHHH 13.9 1.2 47.4 11.48023 3.1658e−11 0.293249 0.026318 14 10 1 3.821 LxxSI CceEE 12.8 1.2 68.5 10.91686 4.6230e−10 0.186861 0.01689 13 14 9 5.25 DxPExL EhHHhH 12.7 1.2 38 10.91795 2.7228e−10 0.334211 0.030355 14 6 1 1 GxSxxN CeChhH 21.5 2 57.9 14.18641 6.8792e−17 0.37133 0.033905 24 20 1 3.231 CxxGxT CccCcC 36.2 3.3 126.6 18.27505 5.0452e−27 0.28594 0.026253 34 24 6 8.695 TLIS EEEE 13.7 1.3 44.6 11.22934 7.1321e−11 0.307175 0.028307 15 1 1 1.601 FPExLT HHHhHH 14.2 1.3 57.9 11.37831 2.9795e−11 0.24525 0.02267 16 4 1 2 DxQAxC HhHHhH 12 1.1 49.1 10.41466 8.3369e−10 0.244399 0.022756 14 4 1 2.023 KxxACK EeeCCC 15.3 1.4 42 11.76957 3.0198e−12 0.364286 0.034205 16 9 1 2.55 LSxxYH HHhhHH 26.5 2.5 52.5 15.58336 4.0718e−21 0.504762 0.047463 26 29 7 6.747 CKNG CCCC 32.8 3.1 60.3 17.22489 5.4973e−26 0.543947 0.0519 30 21 2 7.606 KxVxC EeEcC 19.9 1.9 57.7 13.26771 2.7457e−15 0.344887 0.032977 22 13 1 2.8 PxHxA CcHhH 13.8 1.3 42.8 11.02507 8.4644e−11 0.32243 0.030883 16 9 4 0.688 QTxxR HChhH 18.2 1.8 48.4 12.64218 2.9192e−14 0.376033 0.036274 19 14 2 5.829 KxxxCK EeecCC 17.6 1.7 48.7 12.38274 1.5752e−13 0.361396 0.035054 19 10 1 2.55 SRW CHH 21.5 2.1 52.8 13.57701 2.1455e−16 0.407197 0.040196 23 13 1 2.333 PxxxAL CchhHC 12.4 1.2 28.2 10.32078 4.9428e−10 0.439716 0.043459 12 6 2 0 NQxPxR HHcHhH 12.9 1.3 49.2 10.41678 6.2879e−10 0.262195 0.025975 13 9 1 3.831 KxxAC EeeCC 18.1 1.8 44 12.34444 3.9683e−14 0.411364 0.041254 19 12 1 2.8 KSRW CCHH 15.6 1.6 45.6 11.35132 8.7811e−12 0.342105 0.034653 18 10 1 2.333 DKPxY CCCcC 13.2 1.3 21.2 10.59411 3.0412e−11 0.622642 0.063119 12 15 2 0.154 QxPNR HcHHH 17.2 1.8 47.4 11.86389 4.3286e−13 0.362869 0.037114 18 13 1 5.818 RIxxxQ CCchhH 14.1 1.5 60.7 10.62227 1.3315e−10 0.23229 0.023928 14 14 10 4.532 TMS CEE 18 1.9 61.6 11.97645 2.1832e−13 0.292208 0.030366 20 20 2 4.966 FNTN ECCC 18.2 1.9 37.6 12.12908 3.7927e−14 0.484043 0.05058 13 15 2 6 ACKN CCCC 22.1 2.3 44 13.35197 4.5720e−17 0.502273 0.052665 19 14 1 5.938 SxYQxE ChHHhH 14.9 1.6 34.9 10.89402 1.9565e−11 0.426934 0.044931 12 17 2 0.035 QxNTN CeCCC 17.4 1.8 28.1 11.88416 5.1239e−14 0.619217 0.065309 12 14 1 6 CxNxxT CcCccC 21.3 2.3 79.4 12.86602 4.0656e−15 0.268262 0.028403 20 16 2 5.815 RxxxDS HhheCC 16.7 1.8 45.2 11.42834 2.6297e−12 0.369469 0.039275 18 10 1 5.157 YSTM CCCE 19.6 2.1 42.7 12.43726 1.1609e−14 0.459016 0.04883 21 21 1 4.292 MxxSxN HhhHcC 14.4 1.5 54.6 10.54436 1.5677e−10 0.263736 0.028063 17 7 2 3.311 KPLY CCCC 17.3 1.9 20.1 11.92052 1.7658e−15 0.860697 0.092045 13 18 1 0.511 VxxKNG EccCCC 26.6 2.8 57.3 14.43446 1.7747e−19 0.464223 0.049723 24 14 1 7.438 LxxKxY HhhCcC 22.3 2.4 89.2 13.02413 1.5264e−15 0.25 0.026898 18 12 7 0.583 YxTM CcCE 19.6 2.1 43.7 12.25205 2.0037e−14 0.448513 0.048882 21 21 1 4.292 GSTxE CEEeE 15.9 1.8 28 10.9919 2.4901e−12 0.567857 0.063033 17 10 1 1.048 LxSxxR CcHhhH 20 2.2 79.5 12.06154 5.7006e−14 0.251572 0.028083 23 23 17 0.003 KDYR CCCC 11.5 1.4 21 9.714023 6.6677e−10 0.595238 0.066625 12 8 4 0.333 VAxxNG ECccCC 21.6 2.4 46.6 12.56938 1.5977e−15 0.463519 0.052575 19 13 1 4.438 NVAxK EECcC 24.2 2.7 48.5 13.32393 1.1195e−17 0.498969 0.056658 23 10 1 5.523 YSxM CCcE 23.7 2.8 61.6 12.84049 3.5944e−16 0.38474 0.045127 25 24 2 5.861 TPNR CHHH 22 2.6 54.2 12.38537 1.5783e−15 0.405904 0.047623 22 17 1 9.316 GxxNS CchHH 25.9 3.1 66.8 13.3476 1.3878e−17 0.387725 0.045915 25 16 2 4.171 FPExxT HHHhhH 14.2 1.7 58.9 9.754512 8.2132e−10 0.241087 0.028739 16 4 1 2 DxRExG EeEEcC 14.2 1.7 48 9.784977 5.8536e−10 0.295833 0.035279 14 6 1 1.307 YHxxNE HHhhHH 19.5 2.4 46.3 11.42206 2.0039e−13 0.421166 0.051197 20 20 7 6.268 SxYxxE ChHhhH 23.4 2.9 60.5 12.39716 1.2306e−15 0.386777 0.047559 19 29 4 0.405 MNIF CCHH 20.6 2.5 41.1 11.69437 2.3532e−14 0.501217 0.061842 20 6 1 7.935 MDS ECC 25.5 3.2 83.9 12.7748 2.5660e−16 0.303933 0.037835 24 16 6 5.204 GSxVE CEeEE 15.9 2 34.1 10.18649 3.2680e−11 0.466276 0.058124 17 10 1 1.048 CKxxxT CCcccC 29.6 3.7 96.1 13.6757 1.2906e−18 0.308012 0.038755 30 17 4 6.006 NPTxxE CCChhH 24.1 3 87.4 12.31285 1.9262e−15 0.275744 0.0347 25 27 2 3.167 FxxxxQ EcchhH 21.5 2.7 95.3 11.59038 1.5552e−13 0.225603 0.028396 18 21 10 3.038 MxxSR HhhHC 19.9 2.5 52.1 11.26099 2.7264e−13 0.381958 0.048106 24 12 3 2.21 CGP CHH 24.5 3.1 61.6 12.50142 4.2984e−16 0.397727 0.050135 25 28 11 4.722 KETxxA CCChhH 18.8 2.4 45.1 10.94829 1.1586e−12 0.416851 0.052675 21 22 9 3.218 YHxxN HHhhH 50.5 6.5 81.8 18.01263 3.0622e−71 0.617359 0.07928 34 49 9 15.429 QDKEG HHHHC 23.5 3 53.3 12.12891 1.5706e−15 0.440901 0.056696 22 22 1 4.063 FPExL HHHhH 17.3 2.3 71.5 10.1722 5.1552e−11 0.241958 0.03158 19 8 2 5 QxPxR HcHhH 18.2 2.4 55.2 10.48933 7.0720e−12 0.32971 0.043075 20 15 3 5.831 PGPP CCCC 27.7 3.6 50.4 13.13769 1.2393e−18 0.549603 0.071817 6 23 5 0 STM CCE 24.9 3.3 57 12.3273 3.1613e−16 0.436842 0.057314 26 26 2 4.792 SxxYH HhhHH 55.1 7.3 104 18.27618 2.0986e−73 0.529808 0.070636 39 53 14 16.197 STKVDK CEEEEE 54.6 7.3 226.6 17.8148 7.7075e−70 0.240953 0.032161 61 14 1 4.5 KxVAxK EeECcC 15.3 2 42 9.504713 4.1563e−10 0.364286 0.048679 16 9 1 2.55 VxxxQ CehhH 15.7 2.1 22.7 9.821201 2.0057e−11 0.69163 0.092986 11 16 5 0.045 LGxxI CCeeE 20.7 2.8 131.5 10.8505 2.8269e−12 0.155056 0.020856 21 22 12 6.667 VAxxxG ECcccC 36.9 5 129.3 14.59237 8.2210e−22 0.285383 0.038494 32 20 3 5.755 MxxxxS EecceE 14.3 1.9 28.5 9.210245 6.8755e−10 0.501754 0.067857 14 14 10 0.5 QxNxN CeCcC 17.6 2.4 31.2 10.22307 5.2458e−12 0.564103 0.07679 12 14 1 6 ETGxS ECCcC 17.6 2.4 62 10.0008 6.3892e−11 0.283871 0.038748 20 13 1 6.266 TxDxxR CcHhhH 16.8 2.3 45.8 9.81722 9.5154e−11 0.366812 0.050164 14 21 13 7.167 ExGSS EcCCC 15.6 2.1 54 9.395607 8.4001e−10 0.288889 0.039586 20 15 2 3.386 QxxNK HchhU 17.2 2.4 47.4 9.883211 4.7054e−11 0.362869 0.050001 18 13 1 5.818 PGxxxL CChhhC 18.3 2.5 95.4 10.04912 5.2259e−11 0.191824 0.026518 20 12 4 1 QFN CEC 25 3.5 41.7 12.09169 4.5918e−17 0.59952 0.082983 18 21 3 7 NMxxxE CCchhH 27 3.8 79.7 12.25384 1.9659e−16 0.33877 0.047324 31 20 14 3.042 NxRGxS CeCCeC 15.2 2.1 44 9.190897 9.0030e−10 0.345455 0.048322 17 14 1 4.851 WCG CCH 28.7 4 56.9 12.76874 3.8448e−18 0.504394 0.070649 27 30 12 5.694 VAxKN ECcCC 20.9 2.9 46.7 10.8279 2.6347e−13 0.447537 0.062888 19 13 1 5.188 NQTPN HHCHH 17.4 2.5 46.3 9.80733 5.7989e−11 0.37581 0.052976 17 12 1 5.818 NxGY EcCC 21.7 3.1 58.1 10.9411 2.7368e−13 0.373494 0.05272 23 15 5 7.527 DxPE EhHH 16.3 2.3 38.5 9.514759 1.5307e−10 0.423377 0.059793 19 11 2 2.167 QxNxQ EeCcC 19.3 2.7 36.1 10.43716 9.0830e−13 0.534626 0.075549 17 19 2 1 QDKxG HHHhC 27.2 3.9 57.3 12.29514 4.3110e−17 0.474695 0.067418 23 26 1 4.063 GFTN CCHH 28.4 4 44.3 12.70299 6.0926e−19 0.641084 0.091314 26 19 1 5.255 STVE EEEE 17 2.4 30 9.755365 1.1687e−11 0.566667 0.080927 19 12 2 1.048 QDxEG HHhHC 26 3.7 51.3 11.93412 1.7775e−16 0.487805 0.070194 22 24 1 5.063 LxxxYH HhhhHH 29.3 4.2 149.9 12.33288 2.6305e−16 0.195464 0.028332 29 32 9 6.747 KSxW CChH 17.5 2.5 59.4 9.591293 1.6500e−10 0.294613 0.04278 20 12 3 3.333 PxGPP CcCCC 18.4 2.7 56 9.854107 3.9241e−11 0.328571 0.047758 3 20 3 0 NxAxK EeCcC 24.7 3.6 55.5 11.50343 4.7976e−15 0.445045 0.064834 24 11 2 5.523 MxIF CcHH 24.6 3.6 56.8 11.45787 6.4773e−15 0.433099 0.063193 24 10 3 7.935 GxLxL CcCcH 18.9 2.8 110.4 9.756476 8.9145e−11 0.171196 0.025321 17 19 16 0.071 GxTVE CeEEE 19.5 2.9 45.9 10.09136 6.2818e−12 0.424837 0.062984 21 12 2 1.048 ACxxG CCccC 42.2 6.3 122.4 14.73349 3.9997e−48 0.344771 0.051214 35 26 5 7.116 NxxGxS CecCeC 18.6 2.8 49.7 9.784163 3.5481e−11 0.374245 0.055768 20 17 2 4.851 ExxLxY HhhHhC 17 2.5 69.1 9.239619 4.0465e−10 0.24602 0.036788 23 21 13 6.077 QxQxN CcCeC 16.7 2.5 32.4 9.345434 1.2978e−10 0.515432 0.077204 16 17 2 2 TxNR ChHH 29 4.4 76.1 12.1332 6.1385e−17 0.381078 0.057443 28 24 7 11.983 VxxKxG EccCcC 41.9 6.3 138.2 14.47502 1.6458e−46 0.303184 0.045794 40 22 7 9.791 QxNT CeCC 22.2 3.4 31 10.89491 3.4768e−15 0.716129 0.108225 15 19 1 7 DxxGNG CccCCC 30 4.5 174.5 12.11783 3.3659e−16 0.17192 0.025984 25 27 8 7 FPxxLT HHhhHH 19.4 3 59.9 9.792754 2.7723e−11 0.323873 0.049478 22 8 1 3 FxTN EcCC 19.5 3 66.8 9.782338 3.5580e−11 0.291916 0.044669 15 17 3 6 NxTPN HhCHH 18.4 2.8 46.3 9.571722 5.2061e−11 0.397408 0.060928 18 13 1 5.818 AxKNG CcCCC 22.6 3.5 59.6 10.54578 4.7755e−13 0.379195 0.058531 19 13 1 4.438 DSVT EEEE 20.6 3.2 45.4 10.11567 2.6490e−12 0.453744 0.070196 24 23 2 1.283 NTKVDK CEEEEE 28.8 4.5 135.4 11.72518 2.2882e−15 0.212703 0.032917 33 8 1 5.641 QxKEG HhHHC 24.5 3.8 61.1 10.93374 4.3327e−14 0.400982 0.06247 23 23 2 4.063 STKxDK CEEeEE 55.6 8.7 226.6 16.25592 1.6857e−58 0.245366 0.038248 61 14 1 4.5 STKVxK CEEEeE 58.5 9.1 226.5 16.68499 1.4066e−61 0.258278 0.040286 65 17 1 4.5 NQxPN HHcHH 21.5 3.4 47.3 10.21015 1.1585e−12 0.454545 0.071654 20 16 1 5.828 GSTV CEEE 16.9 2.7 32.9 9.085333 1.8058e−10 0.513678 0.081151 18 11 1 1.048 DxxxGS HhhhCC 20.9 3.3 65.1 9.930092 8.3751e−12 0.321045 0.050797 19 22 13 8.933 YxxxxA HhhccH 22.8 3.6 74.5 10.28525 1.5427e−12 0.30604 0.048945 25 14 5 10.458 SxKVDK CeEEEE 55.6 9 226.6 15.84846 1.0626e−55 0.245366 0.039728 62 15 1 4.5 PPGxP CCCcC 24.9 4.1 88.4 10.60335 2.3088e−13 0.281674 0.045833 11 28 10 1.833 GIPxxQ CCChhH 17.9 2.9 69.3 8.960881 6.8872e−10 0.258297 0.042109 17 17 2 5.263 MDxS ECcC 19.5 3.2 92.2 9.295372 2.0562e−10 0.211497 0.034591 20 13 5 6.204 NQTxN HHChH 17.4 2.9 46.3 8.87643 6.1701e−10 0.37581 0.061769 17 12 1 5.818 WxGP CcHH 27.2 4.5 50.2 11.24573 5.9545e−16 0.541833 0.089269 25 30 10 4.972 DGDxQ CCCcC 26.3 4.4 66.8 10.81102 2.3355e−14 0.393713 0.065788 29 17 3 1.25 STxVDK CEeEEE 58.1 9.7 253.5 15.8352 1.1831e−55 0.229191 0.038304 65 14 1 5.5 QxxTN CecCC 17.9 3 30.2 9.063858 5.9222e−11 0.592715 0.099349 13 15 1 6 TKVDKK EEEEEE 65.1 11 336.5 16.6158 3.4212e−61 0.193462 0.032601 76 17 1 5.808 PFxA CCcH 20.8 3.5 66.6 9.47604 3.8082e−11 0.312312 0.052751 22 13 9 8.396 PPGP CCCC 25.6 4.3 82.9 10.4976 2.2505e−13 0.308806 0.052246 8 30 8 1 SSTKVD HCEEEE 37.4 6.3 196.6 12.53295 3.0773e−35 0.190234 0.032272 49 12 1 4.5 ISxxT CChhH 29.2 5 113.2 11.13658 6.9787e−15 0.257951 0.043782 27 28 14 8.2 LxxNV CchHH 25.9 4.5 77.5 10.45325 1.5252e−13 0.334194 0.057583 22 19 4 1.542 QSPxSL EECcEE 25 4.4 183.2 10.01805 2.8037e−12 0.136463 0.023753 32 15 2 3 LxAxxR CcHhhH 23.3 4.1 144.3 9.678385 1.6775e−11 0.161469 0.028167 28 22 13 8.495 GxxxxN CechhH 25.6 4.5 93.3 10.15598 8.5365e−13 0.274384 0.048505 29 24 4 4.774 QxxxxI EcceeE 27.5 4.9 130.6 10.40287 2.8316e−13 0.210567 0.037539 31 37 19 7 GFxN CChH 31.2 5.6 56.9 11.41646 2.1905e−29 0.54833 0.098116 29 24 3 5.26 NxxC EecC 27.3 4.9 112.3 10.36205 2.4035e−13 0.243099 0.043545 26 14 2 5.944 NxTxN HhChH 18.4 3.3 47.3 8.623012 6.9892e−10 0.389006 0.069712 18 13 1 5.818 RxxxxD EecceE 24 4.3 63.5 9.807516 1.3409e−12 0.377953 0.068037 23 29 16 6.716 NxxGV HhhCC 22.3 4 70.5 9.365085 2.3344e−11 0.316312 0.057231 23 24 20 3.833 RxxM HhhE 19.4 3.5 58.8 8.698453 5.2415e−10 0.329932 0.060173 21 12 2 5.157 AExxxV HHhhcC 21.2 3.9 171 8.898036 3.9391e−10 0.123977 0.022677 27 29 25 6.033 NxKVDK CeEEEE 29.8 5.5 135.3 10.62519 1.1533e−25 0.220251 0.040399 34 8 1 5.641 GLxxxQ CCchhH 54.6 10 239.5 14.37632 3.6957e−46 0.227975 0.041884 60 66 48 3.069 NTKxDK CEEeEE 28.8 5.3 135.4 10.41928 1.0158e−24 0.212703 0.039113 33 8 1 5.641 LxxxxM CchhhH 61.6 11.4 519.7 15.05731 1.4748e−50 0.11853 0.021888 66 64 35 9.681 FxxxxE EcchhH 34 6.3 182.6 11.21745 1.6197e−28 0.186199 0.034562 36 42 30 14.833 SxKVxK CeEEeF 59.8 11.1 226.5 14.98264 4.7717e−50 0.264018 0.049037 67 18 1 4.5 NTxVDK CEeEEE 28.8 5.4 135.9 10.34117 2.2370e−24 0.211921 0.039382 33 8 1 5.641 KQxT CEeE 26.1 4.9 50.9 10.13594 5.6397e−14 0.51277 0.095404 25 25 2 2.517 QxxCS HhhHH 21.4 4 83.1 8.935147 1.8395e−10 0.257521 0.047998 23 13 5 5.023 SxKxDK CeEeEE 56.6 10.6 226.5 14.5105 5.1077e−47 0.24989 0.046621 62 15 1 4.5 LxPxxR CcHhhH 39.9 7.4 228.2 12.08784 5.8061e−33 0.174847 0.032646 47 50 39 5.373 STxVxK CEeEeE 64 12 256.9 15.41759 6.1069e−53 0.249124 0.046526 71 19 1 5.5 GxPxxQ CcChhH 38.5 7.2 136.1 11.99353 1.9062e−32 0.28288 0.052856 41 40 19 6.991 NPxxxE CCchhH 30.1 5.6 135.5 10.53919 2.7481e−25 0.22214 0.041521 33 35 8 6.167 QTPN HCHH 22.1 4.1 46.3 9.249495 8.5114e−12 0.477322 0.089425 22 16 1 7.818 ExGxS EcCcC 22.8 4.3 107 9.131379 8.1828e−11 0.213084 0.040032 25 20 3 6.266 NTKVxK CEEEeE 29.8 5.6 135.4 10.43885 7.8103e−25 0.220089 0.041391 34 9 1 5.641 LSxxxH HHhhhH 34.7 6.5 227.6 11.16265 2.8341e−28 0.15246 0.028772 35 37 13 8.872 FPxxxT HHhhhH 22.4 4.2 81.3 9.076903 7.4347e−11 0.275523 0.052004 24 11 3 3 RxxxxY EecceE 25.3 4.8 101.4 9.579866 5.9796e−12 0.249507 0.047384 25 27 18 8.5 KxxxxY EecceE 31.7 6 126.7 10.69146 5.1661e−26 0.250197 0.047719 32 33 28 10.2 GIxxxQ CCchhH 44.1 8.5 170 12.54746 1.8680e−35 0.259412 0.049891 38 36 14 7.463 QxRxxE CcChhH 21.8 4.2 68.2 8.849948 1.4429e−10 0.319648 0.061734 24 25 8 2.818 LCT CCC 29.6 5.8 90.5 10.25667 5.0074e−24 0.327072 0.063723 26 31 17 11.287 PxVY CeEE 22.7 4.4 581 8.711344 7.2720e−10 0.039071 0.007627 33 23 9 4.01 NPTE CCCH 21.3 4.2 69.4 8.654339 3.0076e−10 0.306916 0.060069 22 18 2 1 STKxxK CEEeeE 60.5 11.8 226.5 14.52276 3.7939e−47 0.267108 0.052292 66 18 1 4.5 MNxF CChH 25.2 4.9 62.4 9.506941 2.2013e−12 0.403846 0.079074 25 7 2 8.023 NVxxK EEccC 25.3 5 66 9.489538 2.9209e−12 0.383333 0.075233 25 12 3 5.523 KNVA EEEC 19.9 3.9 45.1 8.447256 4.0013e−10 0.441242 0.086907 21 17 1 4.181 RxxxTD HcccCC 22.6 4.5 69.1 8.886497 9.5799e−11 0.327062 0.064487 29 27 6 7.032 EAxxAE HHhhHH 21.2 4.2 95.4 8.498906 7.3395e−10 0.222222 0.043919 21 22 20 4.5 VxxxNG EcccCC 29.1 5.8 121.9 9.97096 8.5736e−23 0.23872 0.047201 27 17 3 8.438 RxxxD HhheC 21.4 4.2 67.2 8.614869 3.2608e−10 0.318452 0.063042 24 15 3 7.157 FNT ECC 25.2 5 90.3 9.30099 1.1273e−11 0.27907 0.055319 20 22 4 8 TKxDKK EEeEEE 66.1 13.1 336.4 14.92853 8.7974e−50 0.196492 0.038972 76 17 1 5.808 SSxKVD HCeEEE 38.4 7.7 196.6 11.32751 3.8624e−29 0.19532 0.038973 50 13 1 4.5 TKVxKK EEEeEE 65.1 13 336.5 14.73602 1.5202e−48 0.193462 0.038638 76 17 1 5.808 PxxLxV CceEeE 32.3 6.5 409.9 10.15481 1.1669e−23 0.0788 0.015954 36 29 6 6 YxxxNE HhhhHH 27.3 5.5 107.9 9.499449 8.3765e−21 0.253012 0.051287 28 30 14 7.268 LSxxxQ CChhhH 25.1 5.2 186.8 8.90443 1.9586e−18 0.134368 0.027613 26 30 21 2.125 KExxxA CCchhH 25.3 5.2 85.5 9.049696 5.5135e−19 0.295906 0.061241 26 26 10 3.377 RxxDxD HhhCcC 36.6 7.6 188 10.735 2.5428e−26 0.194681 0.040444 32 30 9 4.792 QxPxSL EeCcEE 27.9 5.8 253.4 9.267533 6.6594e−20 0.110103 0.022941 36 18 2 3.5 SSTxVD HCEeEE 39.7 8.3 215.6 11.14276 2.7999e−28 0.184137 0.038369 52 13 1 5.5 TxVDKK EeEEEE 68.9 14.4 363.1 14.63151 6.3100e−48 0.189755 0.039746 80 17 1 6.808 QSPxxL EECceE 30.2 6.3 250.7 9.604652 2.6407e−21 0.120463 0.025266 39 21 3 3 CxNG CcCC 44.4 9.3 177.5 11.79647 1.4799e−31 0.250141 0.052558 43 35 13 12.179 DKEG HHHC 26.2 5.5 57.6 9.26898 7.4842e−20 0.454861 0.095656 26 26 3 4.063 STKVD CEEEE 61.6 13 230.1 13.90479 2.1619e−43 0.26771 0.056344 67 19 1 5 NxRG CeCC 26.1 5.5 50.1 9.307237 5.3638e−20 0.520958 0.109822 26 24 2 5.991 NIF CHH 25.6 5.4 79.2 9.005026 8.0205e−19 0.323232 0.068183 25 10 3 11.435 SSTKxD HCEEeE 37.9 8 196.6 10.78737 1.3832e−26 0.192777 0.040721 50 13 1 5.5 SxYQ ChHH 24.4 5.2 78.1 8.742181 8.3452e−18 0.31242 0.066298 21 32 5 0.238 QDxxG HHhhC 41.1 8.7 96 11.49502 5.3755e−30 0.428125 0.090888 33 39 7 6.563 TKVDxK EEEEeE 65.5 14 338.5 14.09154 1.4697e−44 0.193501 0.041227 76 17 1 5.808 LPxxxR CChhhH 31.2 6.7 201.9 9.644138 1.7359e−21 0.154532 0.033103 37 37 32 5 NxKxDK CeEeEE 29.8 6.4 135.4 9.482096 8.5112e−21 0.220089 0.047229 34 8 1 5.641 CKxG CCcC 51.5 11.1 173.9 12.55874 1.2519e−35 0.296147 0.063651 47 32 7 11.923 VAxK ECcC 33.3 7.2 90.1 10.14773 1.2188e−23 0.369589 0.079833 30 14 1 6.435 EGxxY ECccC 26.9 5.8 66.1 9.140516 2.2564e−19 0.406959 0.088175 25 23 3 9.785 AxxxGV HhhhCC 45.2 9.8 581.5 11.38712 1.5163e−29 0.077597 0.016857 52 51 43 18.533 QSxxSL EEccEE 25 5.4 183.2 8.519344 5.1349e−17 0.136463 0.029668 32 15 2 3 QxxxxT EecceE 35.6 7.8 134.6 10.29844 2.4065e−24 0.264487 0.057628 35 41 27 8.758 LxPxxQ CcHhhH 26.4 5.8 169.7 8.748374 6.9214e−18 0.155569 0.033949 32 36 24 1 NVA EEC 38.6 8.4 107.2 10.80806 1.0942e−26 0.360075 0.07881 36 26 6 8.273 GFxxxD CCchhH 35.3 7.7 175.1 10.14168 1.1664e−23 0.201599 0.044152 40 44 23 9.865 SxxVDK CeeEEE 59.1 13.1 253.5 13.08031 1.3690e−38 0.233136 0.051524 66 15 1 5.5 TNS HHH 28.8 6.4 113.7 9.14901 1.8584e−19 0.253298 0.056008 26 18 3 4.21 QTxN HChH 22.1 4.9 48.3 8.202911 2.7740e−10 0.457557 0.10135 22 16 1 7.818 GxTN CcHH 32.2 7.1 72.4 9.871338 1.9381e−22 0.444751 0.098713 31 24 4 6.255 NTxVxK CEeEeE 29.8 6.7 140.9 9.196737 1.1483e−19 0.211498 0.047197 34 9 1 5.641 ACK CCC 43.1 9.6 105.9 11.30227 4.3157e−29 0.406988 0.091043 41 25 9 11.66 FxxxxY CchhhC 30.2 6.8 172.7 9.17886 1.3184e−19 0.17487 0.039245 33 31 6 11 SxTKVD HcEEEE 55.5 12.5 313 12.41634 6.4044e−35 0.177316 0.039921 70 18 1 8.833 IxxxxY EcceeE 25.5 5.7 229.8 8.350186 1.9949e−16 0.110966 0.024988 24 28 22 4.5 NxKVxK CeEEeE 30.8 6.9 138.8 9.289826 4.7236e−20 0.221902 0.050018 35 9 1 5.641 NxxPN HhcHH 25 5.6 53.4 8.621938 2.2460e−17 0.468165 0.105585 23 19 1 6.331 WxxxxR CchhhH 33.4 7.5 151.7 9.659593 1.3620e−21 0.220171 0.049712 34 40 29 15.657 ExxxxR EecceE 59.1 13.4 159.8 13.05759 1.8573e−38 0.369837 0.083731 54 72 45 12.861 ACxN CCcC 23.9 5.4 105.8 8.125941 1.3307e−15 0.225898 0.051421 22 18 3 6.049 GxSxxT CcChhH 25.9 5.9 139.5 8.40411 1.2643e−16 0.185663 0.042356 29 23 20 4.411 QxPxxL EeCceE 34.6 7.9 344 9.568532 3.0272e−21 0.100581 0.023093 45 26 4 4.5 FxxxD HhhhC 60.3 13.9 504.8 12.62788 4.1362e−36 0.119453 0.027515 66 69 38 10.725 PxxY EhhH 37.8 8.7 161.4 10.12745 1.2193e−23 0.234201 0.054011 42 43 23 13.599 LxExxR CcHhhH 29.6 6.8 193.1 8.870479 2.0553e−18 0.153288 0.035373 38 40 33 4.292 SxKxxK CeEeeE 64 14.8 237.7 13.17977 3.3609e−39 0.269247 0.062429 69 21 2 4.5 DSxT EEeE 32.3 7.5 89 9.470465 8.5068e−21 0.362921 0.084184 35 37 12 4.36 FPxxL HHhhH 39.1 9.1 187.5 10.21792 4.6988e−24 0.208533 0.048396 46 28 8 9.363 AxxxGI HhhhCC 29.9 6.9 432.7 8.779901 4.3999e−18 0.069101 0.016053 42 42 39 8.841 DxxGDG CccCCC 32.8 7.6 245.6 9.251579 6.0747e−20 0.13355 0.03109 31 37 12 4.958 NQxP HHcH 28.5 6.6 58 9.017809 6.1701e−19 0.491379 0.114435 26 23 3 7.849 QxPN HcHH 26.8 6.3 56.5 8.705318 1.0034e−17 0.474336 0.110806 26 21 2 7.828 GxxL HhhE 23.9 5.6 86.1 7.996979 3.6702e−15 0.277584 0.065047 25 28 21 4.334 FxxxxR CchhhH 53.8 12.6 341.3 11.80788 9.6778e−32 0.157633 0.036994 62 65 53 14.205 ExxxxK HchhhH 29.4 6.9 82.3 8.942929 1.1236e−18 0.35723 0.083914 30 30 22 4 GxxxxQ CcehhH 28.4 6.7 87.1 8.747114 6.3844e−18 0.326062 0.076678 29 37 15 3.502 TKVDK EEEEE 86.3 20.3 363.4 15.07195 6.9306e−51 0.237479 0.055879 98 24 1 10.141 LxxxxQ CchhhH 126.4 29.8 922.6 18.00717 4.5848e−72 0.137004 0.032258 140 158 106 19.556 NQxxN HHchH 21.5 5.1 47.3 7.729667 3.3269e−14 0.454545 0.107054 20 16 1 5.828 LxExxI CcHhhH 31.2 7.4 297.3 8.889427 1.6173e−18 0.104945 0.024787 39 26 16 5.375 VAxxN ECccC 25.5 6.1 95.8 8.160134 9.3058e−16 0.26618 0.063248 25 18 4 7.188 LxxxxR CchhhH 243 57.8 1351.9 24.88539  2.8521e−136 0.179747 0.042782 264 293 196 44.49 PxNV ChHH 25.4 6.1 97.5 8.121634 1.2689e−15 0.260513 0.062064 23 28 9 3.542 TQSPxS EEECcE 21.5 5.1 177.4 7.328957 6.0144e−13 0.121195 0.028944 26 14 2 2 QxxxSL EeccEE 27.9 6.7 256.2 8.321559 2.2276e−16 0.108899 0.026065 36 18 2 3.5 NxxVDK CeeEEE 29.8 7.1 135.8 8.714799 7.8056e−18 0.21944 0.052559 34 8 1 5.641 AxxxxI HhhhcC 71.2 17.1 836.7 13.23487 1.3942e−39 0.085096 0.020406 94 92 85 17.263 NxxHQ HhhHH 21.3 5.1 62.2 7.471413 2.2332e−13 0.342444 0.082215 19 23 10 7.166 STxxDK CEeeEE 59.1 14.2 254.5 12.23358 5.4622e−34 0.23222 0.055962 65 14 1 5.5 VxC EcC 60.4 14.6 326.9 12.28387 2.8734e−34 0.184766 0.044568 54 41 12 14.71 STKxD CEEeE 64.9 15.7 230.1 12.88299 1.5164e−37 0.282051 0.0681 70 22 1 7 PxxxSA CceeEE 21.1 5.1 180.5 7.181197 1.7416e−12 0.116898 0.028284 23 11 3 1.375 NTKVD CEEEE 32.3 7.8 136.3 9.001505 5.8508e−19 0.236977 0.057495 38 10 1 5.641 GVxF CEeE 20.8 5.1 180.9 7.100474 3.1004e−12 0.114981 0.027956 21 22 16 8.469 DLxxxE CCchhH 30.3 7.4 187.5 8.615766 1.7599e−17 0.1616 0.039316 34 38 29 9.749 SxKVD CeEEE 61.6 15.5 231.4 12.64685 3.0755e−36 0.274849 0.066994 68 21 1 5 WxxxY CchhH 20.8 5.1 74 7.236102 1.2256e−12 0.281081 0.06854 19 33 14 8.479 NTKxxK CEEeeE 29.8 7.3 135.5 8.59084 2.2286e−17 0.219926 0.053643 34 9 1 5.641 RxxxxR EecceE 20.5 5 75.5 7.172686 1.9425e−12 0.271523 0.066234 20 25 19 3.583 RxRxG EcCcC 21.8 5.3 79.6 7.390263 3.8620e−13 0.273869 0.066905 22 25 19 4.833 YHxxxE HHhhhH 23.2 5.7 128.6 7.516035 1.4229e−13 0.180404 0.044191 25 26 11 6.411 SSxKxD HCeEeE 38.9 9.5 196.6 9.744738 4.9097e−22 0.197864 0.048527 51 14 1 5.5 HxxNE HhhHH 36.8 9.1 122 9.582928 2.4752e−21 0.301639 0.074219 36 40 15 9.644 LxDxxR CcHhhH 24.5 6 159 7.656071 4.7140e−14 0.154088 0.038 27 31 23 4.616 NxTxxE CcChhH 54 13.3 264.7 11.43435 7.0416e−30 0.204005 0.05034 54 67 29 8.762 TxVxKK EeEeEE 68.9 17 371.5 12.85896 1.8898e−37 0.185464 0.04588 80 17 1 6.808 TKxDxK EEeEeE 66.5 16.5 338.4 12.64344 3.0096e−36 0.196513 0.04865 76 17 1 5.808 RxxDxS EccCcC 20.5 5.1 138.7 6.97113 7.6462e−12 0.147801 0.036621 27 29 20 3.827 QDKE HHHH 23.7 5.9 64 7.716774 3.1832e−14 0.370312 0.091796 22 22 1 4.063 GxxF EccE 28.3 7 152 8.219089 5.0381e−16 0.186184 0.046217 30 34 19 9.566 QSPxS EECcE 30.2 7.5 200.3 8.450279 7.0338e−17 0.150774 0.037434 37 20 3 3 NLxxxD CCchhH 24.9 6.2 242.5 7.619062 6.0600e−14 0.10268 0.025522 26 29 21 11 YxxxxP EecceE 23.8 5.9 118.9 7.53558 1.1961e−13 0.200168 0.049815 27 35 21 2.963 LxExxK CcHhhH 24.2 6 184.2 7.523785 1.2703e−13 0.131379 0.032735 30 32 30 6.2 MxIxE CcHhH 20.5 5.1 117.7 6.943104 9.2565e−12 0.174172 0.043553 25 14 9 8.328 GxExF CcCeE 20.1 5 116.8 6.848623 1.7824e−11 0.172089 0.043222 24 21 4 4.684 GxTxxQ CcChhH 51.1 12.8 261.6 10.9496 1.6032e−27 0.195336 0.049082 63 74 55 7.462 ExxPxD HhcCcC 20.1 5.1 88.6 6.882766 1.4270e−11 0.226862 0.05714 20 24 16 2.25 MNxxD CChhH 22.2 5.6 69.2 7.324761 6.0496e−13 0.320809 0.080818 17 23 13 3.584 FNxN ECcC 20.7 5.2 107.5 6.950636 8.7080e−12 0.192558 0.04852 16 18 5 6 NxCN CcCC 27.4 6.9 110.2 8.055912 1.9302e−15 0.248639 0.062659 28 34 10 5.048 MxxxxP EecceE 21.2 5.3 84.5 7.081721 3.4833e−12 0.250888 0.063298 26 22 9 2.75 FxxxxD EcchhH 20.7 5.2 160.7 6.880946 1.3823e−11 0.128811 0.032525 23 24 16 7.715 RxxxPE HhhcCC 28.5 7.2 111.5 8.193404 6.1741e−16 0.255605 0.064712 30 27 22 3.901 GSxxE CEeeE 20.3 5.1 75.4 6.918189 1.1167e−11 0.269231 0.068279 22 16 6 2.048 NxAL ChHH 30.5 7.7 168.3 8.377216 1.2719e−16 0.181224 0.04598 30 33 27 6.667 SxxVxK CeeEeE 65.3 16.6 303.8 12.30932 1.9144e−34 0.214944 0.054555 73 20 1 5.5 RxxGxA HhhCcC 21.2 5.4 114.5 6.985745 6.6680e−12 0.185153 0.046994 27 33 21 2.833 LTxxxK CChhhH 29.4 7.5 198.1 8.18312 6.3961e−16 0.14841 0.037688 33 33 28 5.063 IxxxxR CchhhH 79.2 20.1 469.1 13.46389 5.9268e−41 0.168834 0.042888 88 90 67 14.891 KNxA EEeC 20.4 5.2 50.6 7.054783 4.4588e−12 0.403162 0.102437 21 17 1 4.181 SLxxxE CCchhH 36.6 9.3 220.9 9.134791 1.5180e−19 0.165686 0.042167 41 46 29 5.65 AxxSQ HhhHC 32.8 8.4 98.7 8.827817 2.6401e−18 0.33232 0.08479 33 27 10 3.798 KxxxLD HhccCC 25.2 6.4 158 7.548711 1.0095e−13 0.159494 0.040754 29 27 16 3.182 VQxxxS ECcccC 25.7 6.6 164.8 7.619327 5.8468e−14 0.155947 0.03985 27 26 2 0.5 FTN CHH 29.5 7.6 58.8 8.553956 3.1605e−17 0.501701 0.128453 27 20 1 5.263 QxxEG HhhHC 34.9 8.9 104.9 9.07013 2.9112e−19 0.332698 0.085314 32 38 8 8.463 GFT CCH 31.4 8.1 73.3 8.717496 7.2684e−18 0.428377 0.109906 30 23 3 5.255 GxDxxQ CcChhH 29 7.4 147.4 8.106973 1.1979e−15 0.196744 0.05051 30 28 20 7.667 LTxxxR CChhhH 30.4 7.8 203.9 8.238198 3.9476e−16 0.149093 0.038329 33 36 29 3.333 DxEG HhHC 38.2 9.8 91.3 9.586215 2.3137e−21 0.418401 0.107564 37 43 13 7.397 NAxxxQ HHhhhH 20.6 5.3 129.5 6.788754 2.5681e−11 0.159073 0.040908 19 23 16 8 QSxxxL EEcceE 30.2 7.8 260.2 8.169296 6.9027e−16 0.116065 0.029863 39 21 3 3 GxSxxA CcChhH 30.1 7.8 260.9 8.142754 8.5659e−16 0.11537 0.029738 32 35 28 9.081 TVxxxE CHhhhH 24.2 6.2 110.1 7.40446 3.0474e−13 0.2198 0.056658 26 20 19 5 SKxxH HHhhH 34 8.8 105.4 8.902407 1.3189e−18 0.322581 0.083153 32 43 14 6.807 CxP ChH 38.6 10 195.9 9.318972 2.6851e−20 0.197039 0.050815 41 47 21 8.789 YxxEN HhhHH 47.1 12.1 158.4 10.43551 4.0653e−25 0.297348 0.076699 47 58 23 3.68 YxxxxE EechhH 27.5 7.1 135.1 7.864945 8.4555e−15 0.203553 0.052558 32 28 16 4.787 SxSxxA CcChhH 28.4 7.3 190 7.931919 4.8305e−15 0.149474 0.038609 34 33 18 4.015 SxxGL HhhCC 27.2 7 120.2 7.839361 1.0445e−14 0.22629 0.058491 31 36 27 3.572 DxAxxQ ChHhhH 30.4 7.9 151.2 8.256938 3.4079e−16 0.201058 0.051986 32 39 30 5.433 ExxxxY EcceeE 29.7 7.7 170.1 8.125602 1.0025e−15 0.174603 0.045189 32 34 27 6.45 ExDxxG HhCccC 20.8 5.4 144.5 6.752501 3.2182e−11 0.143945 0.037384 18 19 7 4 RxKxG EcCcC 27.1 7.1 109.2 7.781732 1.6320e−14 0.248168 0.064822 25 28 18 11.209 TxVDxK EeEEeE 69.3 18.1 368.2 12.32308 1.5043e−34 0.188213 0.049248 80 17 1 6.808 GxxxxF EecceE 33.3 8.7 334 8.43651 6.9899e−17 0.099701 0.026101 45 60 8 3.924 CKN CCC 43.3 11.3 142.4 9.894711 1.0185e−22 0.304073 0.079616 39 34 8 12.606 YxxxE EchhH 25.1 6.6 100 7.466048 1.8730e−13 0.251 0.06584 25 29 20 7.899 AxxxxV HhhhcC 87.4 23 1099.8 13.58946 9.7121e−42 0.079469 0.020879 114 119 101 28.431 LSxxY HHhhH 44.5 11.7 344 9.754079 3.7941e−22 0.12936 0.034022 37 45 14 7.408 TKVxK EEEeE 92.3 24.5 367.4 14.17006 3.0926e−45 0.251225 0.066733 105 29 1 10.141 DxxRN HhhHC 24.5 6.5 74.9 7.38053 3.6042e−13 0.327103 0.086891 26 24 19 6.5 SSTKV HCEEE 41.4 11 198.1 9.427547 9.0951e−21 0.208985 0.055556 52 15 1 4.536 GVxxxE CCchhH 38.3 10.2 238.7 8.992735 5.1079e−19 0.160452 0.042731 43 51 37 5.901 ExxNS HhhHC 18.8 5 57.3 6.447436 2.5887e−10 0.328098 0.087466 18 21 16 3 DxDxT CcCcE 20.6 5.5 97.6 6.635209 7.0133e−11 0.211066 0.05628 18 21 8 6.515 NLY CHH 19.2 5.1 58 6.509825 1.7088e−10 0.331034 0.088392 18 20 17 3 YxGD EeCC 25.4 6.8 119.1 7.343589 4.4620e−13 0.213266 0.057113 29 28 21 7.501 SxxWPS CccCCC 19.8 5.3 161.2 6.396654 3.2879e−10 0.122072 0.032719 23 22 1 4 ELxxxE CCchhH 27.3 7.3 172.9 7.544366 9.5073e−14 0.157895 0.042349 28 29 21 2 SxTxVD HcEeEE 57.7 15.5 332.4 10.97081 1.1028e−27 0.173586 0.046666 73 19 1 9.833 TxxDKK EeeEEE 69.9 18.8 364 12.10562 2.0737e−33 0.192033 0.05163 80 17 1 6.808 SAGT CCCC 18.8 5.1 65.4 6.36097 4.4071e−10 0.287462 0.077343 20 24 9 6.186 NPxE CCcH 23.8 6.4 92.8 7.124827 2.1574e−12 0.256466 0.069004 25 21 5 1 TQxPxS EEeCcE 25.8 6.9 245.4 7.260776 7.8442e−13 0.105134 0.028289 32 17 2 2.5 DxSV EeEE 19.1 5.1 128.3 6.281303 6.9655e−10 0.14887 0.040088 22 19 16 2.25 GVxxxD CCchhH 23.4 6.3 189.3 6.92795 8.7577e−12 0.123613 0.033287 24 27 22 6.057 QxxxxT CccecC 24.6 6.6 81.9 7.279091 7.3895e−13 0.300366 0.080963 28 27 10 2.904 RxxxxT EecceE 23.5 6.4 116.1 6.994801 5.5755e−12 0.202412 0.054742 20 27 19 8.114 YxxxNR EcccEE 19.8 5.4 85.3 6.438949 2.5510e−10 0.232122 0.062882 21 18 2 4.356 NKxG HHhC 32.2 8.7 87.3 8.377682 1.2095e−16 0.368843 0.099933 33 36 27 4.171 CxH ChH 22.2 6 117.7 6.772808 2.6270e−11 0.188615 0.051121 24 22 17 5 NVM HHH 22.3 6 170.9 6.72985 3.4499e−11 0.130486 0.035381 22 16 4 3.542 ExxI HhhE 29.5 8 120.6 7.861338 8.0506e−15 0.24461 0.06639 31 36 25 5.111 STxVD CEeEE 66.1 17.9 259 11.78422 9.9807e−32 0.255212 0.069278 72 20 1 6 KVDKK EEEEE 71.2 19.4 341.6 12.13106 1.4989e−33 0.208431 0.056672 81 22 1 5.808 SGxW CCcE 20.7 5.6 91.2 6.551699 1.1925e−10 0.226974 0.06179 21 23 18 7.5 NTxxDK CEeeEE 28.8 7.8 135.9 7.708178 2.6509e−14 0.211921 0.057719 33 8 1 5.641 DxVT EeEE 24.9 6.8 171 7.088115 2.7435e−12 0.145614 0.039734 31 34 9 1.708 YNN ECC 19.7 5.4 60.5 6.472367 2.0995e−10 0.32562 0.088854 17 26 9 6.123 PxTxxQ CcChhH 21.7 5.9 173.7 6.591601 8.7031e−11 0.124928 0.034126 30 33 20 5.625 GxxGF HhhCC 22.1 6 100.2 6.742831 3.2248e−11 0.220559 0.060261 29 16 6 4.16 LDxxxR CChhhH 32.5 8.9 240.5 8.068869 1.4172e−15 0.135135 0.036966 38 32 13 6.644 NxKVD CeEEE 34.1 9.4 138.3 8.361157 1.2840e−16 0.246565 0.067811 41 12 1 5.641 STxxxK CEeeeE 68 18.7 273.9 11.80545 7.5425e−32 0.248266 0.06831 74 22 3 5.5 ExxHD HhhllH 21.8 6 82.4 6.70029 4.3412e−11 0.264563 0.072797 21 22 13 5.667 DxNxY CcCcE 20.3 5.6 84.7 6.441134 2.4504e−10 0.239669 0.065956 24 17 7 1.375 DxxGxP HhhCcC 33.8 9.3 183 8.241246 3.4292e−16 0.184699 0.050855 38 39 19 4.333 SxxxxN CceccE 20.4 5.6 67.2 6.515335 1.5374e−10 0.303571 0.083593 25 26 5 5.606 FxxM ChhH 32.3 8.9 164.3 8.052618 1.6312e−15 0.196592 0.054268 37 32 17 8.547 SPSSL ECCEE 22.6 6.2 113.2 6.737919 3.2449e−11 0.199647 0.05512 25 10 1 0 WxxxxT HhhccC 21.1 5.8 171.2 6.436797 2.3915e−10 0.123248 0.034041 27 24 20 3.9 ESY EEE 19.3 5.3 85.3 6.240198 8.9001e−10 0.22626 0.062595 17 20 10 8.5 SxTKxD HcEEeE 56 15.5 313 10.55562 9.5006e−26 0.178914 0.049499 71 19 1 9.833 VxxKN EccCC 29.4 8.2 105.5 7.747512 1.9363e−14 0.278673 0.077267 28 18 3 8.188 GxxxDF EeccEE 25.3 7 248.3 6.995039 5.0997e−12 0.101893 0.028291 34 35 3 0 RxxxTG EeccCC 24.8 6.9 127.8 7.018198 4.4794e−12 0.194053 0.053883 30 33 18 1.284 VxxGA HhcCC 33.4 9.3 235.9 8.076537 1.2963e−15 0.141585 0.039348 39 40 37 4.283 QxPxS EeCcE 34.5 9.6 273.2 8.163922 6.2295e−16 0.126281 0.035226 43 23 3 3.5 LxxxxK CchhhI-J 149.3 41.7 947.4 17.0475 7.0481e−65 0.157589 0.043999 173 204 157 23.953 SxAxxR ChHhhH 47.9 13.4 257.1 9.69243 6.3584e−22 0.186309 0.052044 49 50 24 4.47 ExxxxL EecceE 40.3 11.3 277.3 8.826998 2.0686e−18 0.14533 0.040651 35 41 22 9.5 YxxxxY EcceeE 26 7.3 256.4 7.038223 3.6866e−12 0.101404 0.028396 31 34 24 10.368 NxSxxD CcChhH 25.1 7 145.6 6.979942 5.7351e−12 0.17239 0.048331 28 28 22 4.334 PGxxA CChhH 28.5 8 157.5 7.44514 1.8844e−13 0.180952 0.050747 32 27 20 2.951 LSxxxI CChhhH 25.4 7.1 404.3 6.907684 9.1681e−12 0.062825 0.017623 27 30 22 3.343 PNR IHHI 26.3 7.4 104.2 7.227147 9.8791e−13 0.252399 0.070802 28 23 6 10.321 FxxEE HhhHH 21.3 6 123.9 6.403548 2.9275e−10 0.171913 0.048423 23 25 19 5.976 RxHG HhHC 25.6 7.2 82.9 7.166051 1.5713e−12 0.308806 0.086994 32 33 30 6.25 QxxxxL EecceE 42.9 12.1 459.9 8.96776 5.6147e−19 0.093281 0.026328 53 36 12 5.5 RxxxGL HhhhCC 28.6 8.1 176.7 7.393568 2.7275e−13 0.161856 0.045701 32 34 21 5.7 GLxxxE CCchhH 55.6 15.7 370.9 10.28661 1.5314e−24 0.149906 0.042345 55 64 53 14.726 DxxRG CceCC 21.2 6 58.3 6.559553 1.1201e−10 0.363636 0.102768 24 19 1 4.782 YxxxxK EecceE 23.2 6.6 106.7 6.708479 3.8350e−11 0.217432 0.061457 25 30 21 4.75 FxxS ChhH 46.5 13.2 250.8 9.432711 7.6287e−21 0.185407 0.052529 51 43 21 7.676 TQxG HHcC 23.6 6.7 73 6.85765 1.4179e−11 0.323288 0.091676 26 32 21 3.847 SxKxD CeEeE 66.9 19 237.4 11.47017 3.6870e−30 0.281803 0.079926 71 24 1 7 SxxWxS CccCcC 23.6 6.7 200.2 6.644325 5.6746e−11 0.117882 0.033448 26 26 4 6 VPS CHH 23.5 6.7 71.3 6.843087 1.5709e−11 0.329593 0.093573 20 23 13 6 FxxxLT HhhhHH 24 6.8 425 6.631623 6.0285e−11 0.056471 0.016048 27 14 6 5.5 SSTxxD HCEeeE 40.2 11.4 216.6 8.739729 4.4322e−18 0.185596 0.052797 53 14 1 6.5 YDY CCE 24.7 7 113 6.871379 1.2210e−11 0.218584 0.062322 22 28 12 4.25 LSxxxR CChhhH 40.4 11.5 293.2 8.662063 8.5519e−18 0.13779 0.039389 48 58 43 12.646 EQF CEE 23.4 6.7 79.4 6.738533 3.1440e−11 0.29471 0.084441 26 26 4 4.684 TxVDK EeEEE 90 25.8 396 13.07771 8.3835e−39 0.227273 0.065121 102 24 1 11.141 ETxS ECcC 29.2 8.4 99.1 7.526295 1.0238e−13 0.294652 0.084439 27 26 9 13.54 LxxGY HhcCC 25.2 7.2 158.7 6.845655 1.4142e−11 0.15879 0.045521 24 29 23 9.094 TKVxxK EEEeeE 66 18.9 393 11.08834 2.6474e−28 0.167939 0.048171 77 18 2 5.808 IAxxG HHhhC 23.8 6.8 183.8 6.617026 6.7222e−11 0.129489 0.037163 25 31 22 2.501 LxxxGV HhhhCC 23 6.6 445.9 6.430108 2.2726e−10 0.051581 0.014805 27 29 25 6.833 YxxM CccE 28.9 8.3 165.3 7.338177 4.0315e−13 0.174834 0.050202 31 30 8 7.862 MxxxxY CchhhH 22.2 6.4 219.9 6.355883 3.7539e−10 0.100955 0.029014 23 26 20 2 NxxxxT EccccE 26.5 7.6 179.9 6.984374 5.2547e−12 0.147304 0.04239 30 37 20 1.106 TxAxxK ChHhhH 33.7 9.7 179.1 7.910811 4.7461e−15 0.188163 0.054259 35 37 26 1.106 WxxxxK HhhhcC 38.8 11.2 266.7 8.429782 6.3105e−17 0.145482 0.041973 47 49 29 6.095 PxSS EhHH 21.2 6.1 94.8 6.304806 5.4447e−10 0.223629 0.064531 24 25 4 3.333 TKxDK EEeEE 87.3 25.2 364.3 12.81001 2.7096e−37 0.239638 0.069249 98 24 1 10.141 QxKxG HhHhC 36 10.4 188.4 8.142734 7.1133e−16 0.191083 0.055388 34 36 11 5.063 SxxKVD HceEEE 56.5 16.4 313 10.17234 4.8080e−24 0.180511 0.052395 71 19 1 8.833 IDxS ECcE 41.4 12 221.9 8.712627 5.4346e−18 0.186571 0.054175 49 41 2 4.361 PTxxxL CChhhH 23 6.7 322.9 6.377182 3.1697e−10 0.071229 0.0207 23 22 12 4.833 FxxH CccH 21 6.1 86.6 6.254237 7.5023e−10 0.242494 0.070478 21 16 10 0.021 LxxxxP EecceE 22.6 6.6 152.9 6.393634 2.9287e−10 0.147809 0.042963 25 27 20 4.5 RxxxxE EecceE 36.6 10.6 131.4 8.30223 1.9387e−16 0.278539 0.080969 44 52 39 10.524 QTxxxK HHhhhH 25.6 7.4 144 6.832254 1.5255e−11 0.177778 0.051705 24 28 17 4.636 LxxxxV HccccE 24.2 7 365.7 6.531652 1.1388e−10 0.066174 0.019247 26 26 21 4.9 DxNxE CcChH 25.1 7.3 128.5 6.781685 2.1820e−11 0.195331 0.056827 25 31 20 4.226 TxTxxE CcChhH 30.8 9 191.4 7.468604 1.4651e−13 0.16092 0.046846 35 33 29 6.084 TKxxKK EEeeEE 66.1 19.3 341.6 10.99212 7.5992e−28 0.193501 0.056354 76 17 1 5.808 MNxxE CChhH 44.6 13 167.5 9.123343 1.3666e−19 0.266269 0.077633 46 33 16 9.479 ExxxxR EcceeE 39.2 11.5 139.1 8.542044 2.4730e−17 0.281812 0.082523 39 47 29 4.741 ANxxN HHhhH 26.8 7.9 128.3 6.978653 5.4345e−12 0.208885 0.061203 29 34 25 6.133 NxxxxW CccccE 25.7 7.5 182.6 6.748517 2.6433e−11 0.140745 0.041333 26 33 18 9.452 ExxGxS HhcCcC 24.9 7.3 129.6 6.68272 4.2194e−11 0.19213 0.056545 27 30 23 9.63 QxxxxM CcchhH 24.2 7.1 154 6.5474 1.0378e−10 0.157143 0.046288 27 21 12 1.75 ExxGxS HhhCcC 35.4 10.4 185.6 7.959755 3.0861e−15 0.190733 0.056187 37 39 35 7.367 VxxxxF CchhhH 40.9 12.1 688.2 8.38324 8.7602e−17 0.05943 0.017513 51 68 39 1.633 LSxxxK CChhhH 29.4 8.7 241 7.163028 1.3727e−12 0.121992 0.036016 33 42 31 5.338 MNI CCH 22.6 6.7 70.6 6.475222 1.7836e−10 0.320113 0.094588 23 9 4 8.685 GxSxxE CcChhH 92.3 27.3 563.9 12.76202 4.6873e−37 0.163682 0.048374 106 122 100 25.005 SxxxDK CeeeEE 60.1 17.8 256.6 10.37493 5.7844e−25 0.234217 0.069505 66 15 1 5.5 NxAxxK ChHhhH 23.7 7.1 137.1 6.437742 2.1271e−10 0.172867 0.051429 26 30 19 6.25 SPxSL ECcEE 42.9 12.8 185.7 8.74043 4.1484e−18 0.231018 0.068739 49 26 2 4 QxTG HhHC 36.3 10.8 146.5 8.059476 1.3787e−15 0.247782 0.073749 40 36 23 9.267 NxKxxK CeEeeE 32.2 9.6 154 7.535957 8.5785e−14 0.209091 0.062307 37 12 3 5.641 NTKxD CEEeE 32.3 9.6 139.1 7.572258 6.5452e−14 0.232207 0.069229 38 10 1 5.641 YxxxF HhhcC 33.4 10 178.8 7.634612 3.9592e−14 0.186801 0.055774 31 41 27 14.079 GRxxxE CCchhH 25.7 7.7 147.8 6.68039 4.1501e−11 0.173884 0.051943 31 30 28 5.267 LPxxV CChhH 31.7 9.5 328.1 7.31376 4.3680e−13 0.096617 0.028935 31 31 18 5.61 ExxxxV EcceeE 46.8 14 318.4 8.939876 6.6359e−19 0.146985 0.044109 54 55 39 6.26 AxxxGA KhhhCC 26.9 8.1 511.8 6.675596 4.0624e−11 0.052152 0.015659 32 38 29 11.774 RxxL HhhE 32.4 9.7 158.9 7.491324 1.1856e−13 0.203902 0.061321 35 36 19 3.333 AxxGxP HhcCcC 32.9 9.9 247.6 7.451189 1.5600e−13 0.132876 0.040039 40 44 34 7.278 FxxxxK CchhhH 35.7 10.8 264.1 7.751308 1.5295e−14 0.135176 0.040809 41 45 36 8.614 QTP HCH 22.1 6.7 47.9 6.42922 2.4745e−10 0.461378 0.139514 22 16 1 7.831 KxxGF HhcCC 37.3 11.3 204.8 7.969461 2.7196e−15 0.182129 0.055082 44 44 34 8.977 NTxVD CEeEE 31.3 9.8 136.8 7.475662 1.3386e−13 0.236111 0.071465 38 10 1 5.641 SSxxVD HCeeEE 40.7 12.3 215.6 8.311402 1.6093e−16 0.188776 0.057261 53 14 1 5.5 GxSxxQ CcChhH 32.5 9.9 203.2 7.392465 2.4290e−13 0.159941 0.048517 38 46 32 3.241 MxxxxL HhhccC 37.8 11.5 525 7.853004 6.6035e−15 0.072 0.021871 46 52 41 8.19 NxLP HhCC 31.4 9.5 153.2 7.304107 4.7698e−13 0.204961 0.062314 35 40 29 7.155 DxxSN HhhHH 31 9.4 133.5 7.288476 5.4139e−13 0.23221 0.070612 29 34 21 3.4 DRC CCC 32.2 9.8 128.7 7.444459 1.6904e−13 0.250194 0.076146 35 28 13 11.164 ExxxxK EcceeE 43.1 13.1 168.8 8.606301 1.3067e−17 0.255332 0.077849 46 60 39 3.758 RxxFV HhhHH 24.5 7.5 193.4 6.343231 3.7108e−10 0.12668 0.038702 26 20 5 3.886 HxxxxR CchhhH 42.2 12.9 198.2 8.441254 5.3279e−17 0.212916 0.065049 44 48 33 16.485 SxxDS HhhHH 28.9 8.9 121.4 6.997453 4.4603e−12 0.238056 0.072925 31 35 29 6.813 SxW ChH 89.6 27.5 434.3 12.254 2.6846e−34 0.206309 0.063216 84 91 42 39.624 TxSxxE CcChhH 26.4 8.1 188.8 6.57813 7.8469e−11 0.139831 0.042863 31 34 29 3.467 ExxLP HhhCC 31.6 9.7 176.5 7.229156 8.0852e−13 0.179037 0.054991 30 32 26 7.579 ExxxxT EecceE 36.9 11.3 146.3 7.899199 4.7926e−15 0.252221 0.07755 41 43 32 7.786 TQA CHH 28.7 8.8 79.5 7.084686 2.4870e−12 0.361006 0.111203 29 33 24 7.459 YxxxxQ EccccC 41.7 12.9 277.2 8.238435 2.8485e−16 0.150433 0.046375 43 47 27 9.222 RIxxN HHhhH 31.3 9.7 211.7 7.132289 1.6125e−12 0.147851 0.045594 32 23 15 10.306 DxSQ EcCC 24.6 7.6 83.1 6.463222 1.7704e−10 0.296029 0.091555 23 25 12 3.077 RxxGI HhcCC 41 12.7 265.2 8.142027 6.3123e−16 0.1546 0.047865 52 60 49 6.078 KxxGxN HhcCcC 33.4 10.3 186.4 7.375182 2.6922e−13 0.179185 0.055503 38 41 22 3.053 ExxAA HhhHC 52.1 16.1 21.4 9.306055 2.2237e−20 0.243458 0.075445 64 66 52 8.575 SxxxxY HhhccC 32.3 1.0 223.4 7.202382 9.5601e−13 0.144584 0.044849 33 37 30 10.279 WxxP CchH 45.8 14.2 136.8 8.84778 1.5505e−18 0.334795 0.103937 44 60 23 12.363 ExxxAL HhhhHC 32.2 10 257.3 7.160501 1.2869e−12 0.125146 0.038867 37 36 30 1.667 RxxxD CechH 23.6 7.4 54.6 6.44067 2.1538e−10 0.432234 0.134677 22 29 8 2.167 AxxxGL HhhhCC 28.1 8.8 473.3 6.596022 6.5719e−11 0.05937 0.018507 34 33 33 6.75 WxG CcH 47.8 14.9 153.6 8.967722 5.1676e−19 0.311198 0.097025 43 51 23 13.556 ExSxxE CcChhH 46.7 14.6 297.5 8.631726 9.6940e−18 0.156975 0.048973 50 50 40 11.231 RxxI HhhE 27 8.4 142.7 6.580268 7.6218e−11 0.189208 0.059204 28 28 18 4.75 KxF CeC 35.5 11.1 146.1 7.608196 4.5904e−14 0.242984 0.076091 40 51 16 6.317 TxAxxR ChHhhH 26 8.1 178.9 6.402991 2.4282e−10 0.145333 0.045534 26 30 25 5.688 AxGxR HcCcC 36.6 11.5 170.4 7.680274 2.5874e−14 0.214789 0.06734 42 47 39 10.232 RxxGxN HhcCcC 27.5 8.6 166 6.600575 6.5622e−11 0.165663 0.051959 32 37 18 2 LxxxxI CchhhH 120.9 37.9 1893.1 13.6104 5.3167e−42 0.063864 0.020034 139 130 97 17.117 EDxxY HHhhH 34.2 10.8 168.1 7.391077 2.3540e−13 0.20345 0.063963 35 37 20 1.694 NxxSL HhhHH 28.2 8.9 193.6 6.646094 4.7656e−11 0.145661 0.045803 30 31 23 5.507 LNxxQ CChhH 24.6 7.7 175.6 6.199337 8.9664e−10 0.140091 0.04407 27 29 23 9.015 KxDKK EeEEE 72.2 22.8 341.6 10.7017 1.5998e−26 0.211358 0.066796 81 22 1 5.808 KxxGA HhcCC 44 13.9 283.3 8.262977 2.2260e−16 0.155312 0.049167 55 68 45 5.091 TxAxxE ChHhhH 42.1 13.3 254.5 8.093575 9.1094e−16 0.165422 0.052386 46 44 34 5.667 VxxxxQ CchhhH 41.1 13 292.8 7.955165 2.7819e−15 0.140369 0.044502 47 59 39 8.622 DSV EEE 27 8.6 127.2 6.521739 1.1133e−10 0.212264 0.067344 32 31 8 3.083 GxxxxQ CcchhH 255.1 81.2 1223.1 19.98054 1.2830e−88 0.208568 0.066361 268 302 205 46.327 SxxxxV HhhhcC 35.4 11.3 332.5 7.310744 4.0564e−13 0.106466 0.033905 46 47 40 7.398 NxxRN HhhHH 33.2 10.6 140.1 7.23656 7.3844e−13 0.236974 0.075474 37 38 27 5.133 YxxxN HhhhH 359.7 114.6 1469.5 23.8353  2.2944e−125 0.244777 0.078017 311 417 220 77.817 SAxxxR CHhhhH 38.1 12.2 224.6 7.644138 3.2710e−14 0.169635 0.054175 38 37 21 5.834 EGxT ECcE 26.5 8.5 78 6.552315 9.4222e−11 0.339744 0.10876 28 30 15 1.51 LxxxxY CchhhH 42 13.5 555.3 7.880036 4.8923e−15 0.075635 0.024224 52 50 41 8.542 TxxxxW CchhhH 26.8 8.6 193.7 6.357807 3.1394e−10 0.138358 0.044331 32 27 13 9.251 ExxxxP EecceE 34.5 11.1 144.7 7.333049 3.5729e−13 0.238424 0.076446 38 41 32 2.484 AxxxxR CchhhH 115.3 3.7 706.6 13.22827 9.2344e−40 0.163176 0.052343 125 142 105 26.714 LGF HCC 32.9 10.6 200.8 7.063506 2.5027e−12 0.163845 0.052585 37 40 32 5.018 ITxxQ CChhH 28.7 9.2 189 6.582122 7.1234e−11 0.151852 0.04875 34 34 28 11.232 TxxxxR CchhhH 97.2 31.2 509.4 12.1895 5.4680e−34 0.190813 0.061279 107 125 93 23.513 STKV CEEE 69.5 22.3 234.9 10.49468 1.4747e−25 0.295871 0.095048 75 24 1 5.036 IxxxxY CchhhH 27.2 8.7 372.9 6.318022 3.9509e−10 0.072942 0.02344 36 36 36 7.75 SPxxLS ECceEE 30 9.7 170.2 6.744862 2.3659e−11 0.176263 0.056698 35 22 2 1 ALS EEE 27 8.7 349.5 6.287868 4.7936e−10 0.077253 0.024873 30 29 17 1.825 FxxxE EehhH 30.6 9.9 170.7 6.807095 1.5366e−11 0.179262 0.057738 35 38 21 7.082 SxxxxQ CchhhH 107.1 34.6 557.3 12.73468 5.8204e−37 0.192177 0.062044 123 129 80 29.468 SxxPG HhcCC 30 9.7 107.9 6.839335 1.2706e−11 0.278035 0.089798 34 38 14 6.743 TVA CHH 40.3 13 137 7.949197 3.0102e−15 0.294161 0.095013 42 40 29 10.153 KxHG HhHC 25.4 8.2 85.6 6.310346 4.4829e−10 0.296729 0.095898 29 33 23 6.286 DxPxY CcCcC 26.5 8.6 158 6.299163 4.5765e−10 0.167722 0.05423 26 30 15 2.875 SSTxV HCEeE 44.7 14.5 217.1 8.214938 3.2657e−16 0.205896 0.066745 56 16 1 5.536 SSxKV HCeEE 42.6 13.8 198 8.026654 1.5452e−15 0.215152 0.0698 54 17 1 4.536 NTxxxK CEeeeE 33.8 11 168.6 7.116682 1.6931e−12 0.200474 0.065182 38 13 4 6.141 LPxxQ CChhH 26 8.5 150.9 6.209625 8.0645e−10 0.1723 0.056038 27 29 24 6.067 SxTxxE CcChhH 26.3 8.6 179.1 6.210132 7.9457e−10 0.146845 0.047823 35 32 21 6.641 PxSQ ChHH 31.3 10.2 111 6.920163 7.0916e−12 0.281982 0.092073 33 39 25 6.917 YxxxxR EccceE 42 13.7 199.7 7.912163 3.8543e−15 0.210315 0.068697 48 46 8 9.456 PxxLT HhhHH 34.7 11.3 229.3 7.111345 1.7124e−12 0.15133 0.049482 34 19 6 4.5 WxxxxK CchhhH 33.1 10.8 143.7 7.034008 3.0769e−12 0.230341 0.075405 39 43 23 7.556 SxTKV HcEEE 63.7 20.9 316.4 9.703558 4.3917e−22 0.201327 0.065941 79 26 1 9.869 WxxxE CchhH 64.8 21.2 274 9.845227 1.0984e−22 0.236496 0.077482 62 77 54 16.611 YxxxH HhhhC 112.7 36.9 440.2 13.02159 1.4162e−38 0.25602 0.083929 129 149 109 34.612 SAxxxK CHhhhH 30 9.9 163.6 6.620898 5.3547e−11 0.183374 0.060226 32 39 22 6 PVxxA HHhhH 42.9 14.1 430.6 7.802016 8.8311e−15 0.099628 0.03273 42 46 28 3.2 LxxxxI HhhccC 81.5 26.8 1641 10.66137 2.1892e−26 0.049665 0.016319 99 104 90 18.507 NxxxDK CeeeEE 29.8 9.8 140.6 6.628627 5.1332e−11 0.211949 0.069648 34 8 1 5.641 SxLP HhCC 41.8 13.8 235.1 7.791006 9.8874e−15 0.177797 0.058524 47 57 38 5.326 IxxxxN CcchhH 27.4 9.1 214.6 6.232302 6.7019e−10 0.127679 0.042173 29 30 18 4.045 KVDxK EEEeE 71.7 23.7 345.2 10.22337 2.3244e−24 0.207706 0.068609 81 22 1 5.808 NxV HhE 37.2 12.3 189.2 7.349348 2.9702e−13 0.196617 0.064947 37 44 26 9.9 AxGF HcCC 33.5 11.1 222.8 6.917099 6.7617e−12 0.150359 0.049674 39 40 32 6.281 VxxxxV EcceeE 36.6 12.1 520 7.116802 1.5683e−12 0.070385 0.023302 36 40 28 10.501 DxAxxD ChHhhH 28.7 9.5 168.1 6.409489 2.1528e−10 0.170732 0.056547 34 38 32 4.5 DxDGxG CcCCcC 35.9 11.9 416.7 7.054973 2.4585e−12 0.086153 0.028573 36 39 13 4.333 TxxxxT EecceE 82.4 27.3 361.9 10.95296 9.5962e−28 0.227687 0.075539 88 97 64 17.615 QxxxxQ CchhhH 45.1 15 238.9 8.045709 1.2643e−15 0.188782 0.062644 46 53 35 8.666 DGR HCC 24.9 8.3 59.6 6.223041 7.9087e−10 0.417785 0.138959 28 31 21 4.046 RxxxxH HhhccC 65.2 21.7 297.8 9.703437 4.3224e−22 0.218939 0.072826 71 77 61 18.915 TDV CCH 28.4 9.5 124.7 6.397493 2.3547e−10 0.227747 0.075963 31 33 12 5.485 ExxGA HhhCC 41.1 13.7 243.7 7.613209 3.8832e−14 0.16865 0.056268 48 61 43 5.717 GST CEE 28 9.3 96.7 6.422618 2.0456e−10 0.289555 0.096607 28 25 8 4.048 SxxxxR CchhhH 124.8 41.7 647.7 13.30661 3.0825e−40 0.192682 0.064369 133 159 109 32.489 QSxxS EEccE 30.2 10.1 204.5 6.487393 1.2578e−10 0.147677 0.049385 37 20 3 3 AxxQG HhhHH 30.2 10.1 218 6.47422 1.3671e−10 0.138532 0.046347 31 36 15 1.13 YxGS EcCC 36.1 12.1 183.1 7.135684 1.4043e−12 0.19716 0.06612 43 46 24 11.261 AxxGL HhhCC 41.1 13.8 280.1 7.540236 6.6990e−14 0.146733 0.049246 46 50 40 9.057 QxxxW HhhhH 165.8 55.6 973.5 15.20679 4.5631e−52 0.170313 0.057164 158 184 121 37.643 HxxxxS HhhhcC 31.5 10.6 219.9 6.594011 6.1157e−11 0.143247 0.048099 34 40 30 7.333 TxAxxQ ChHhhH 35.1 11.8 204.9 6.994651 3.8335e−12 0.171303 0.057525 42 42 19 4.784 TAxxxE CHhhhH 29.1 9.8 179.3 6.350328 3.0867e−10 0.162298 0.054574 37 31 25 1.668 MxxxxR CchhhH 51.3 17.3 353 8.401305 6.2683e−17 0.145326 0.048896 65 72 61 7.795 TxAQ ChHH 65.5 22 303.2 9.611531 1.0400e−21 0.216029 0.072705 74 76 61 10.824 ANxP HHcC 30.6 10.3 110 6.640679 4.6760e−11 0.278182 0.093685 28 34 24 2.667 YxxxM CchhH 28.1 9.5 219.6 6.178173 9.1504e−10 0.12796 0.043199 30 35 21 11.567 GxxxxY CcchhH 68.3 23.1 533.9 9.630341 8.3399e−22 0.127927 0.043196 66 80 46 32.127 NxxVxK CeeEeE 31.3 10.6 203.1 6.545306 8.4370e−11 0.154111 0.052072 36 10 2 5.641 DxxIN HhhHH 34.4 11.6 212.9 6.864841 9.4633e−12 0.161578 0.054645 43 43 33 1.163 NxxxN HhchH 28.5 9.7 69.5 6.537397 9.8303e−11 0.410072 0.138884 28 24 6 6.331 RxNG EeCC 51.7 17.5 171.1 8.620737 9.9272e−18 0.302162 0.102376 46 56 34 12.172 TxxDxK EeeEeE 71.3 24.2 396.7 9.891898 6.4050e−23 0.179733 0.060932 81 18 2 6.808 ARxP HHcC 39.6 13.4 140.5 7.511607 8.6527e−14 0.281851 0.095553 42 50 39 3.827 SxAxxA ChHhhH 31.9 10.8 324.7 6.517178 9.9192e−11 0.098245 0.033327 43 44 40 8.897 LxxTG HhhHC 31.7 10.8 282.8 6.51068 1.0405e−10 0.112093 0.038036 35 37 21 11.255 QCG CCC 28.6 9.7 138.1 6.276235 4.9829e−10 0.207096 0.070437 30 33 17 12.384 RSxxE CChhH 37 12.6 179.8 7.134674 1.3888e−12 0.205784 0.070013 40 44 39 8.156 WxxxN HhhhC 95 32.4 413 11.46138 2.9542e−30 0.230024 0.078414 111 120 80 19.341 FxxxR HhhhC 77.3 26.4 401.6 10.25513 1.5834e−24 0.19248 0.065697 84 99 66 13.27 KVxKK EEeEE 71.2 24.3 349.6 9.858861 8.8905e−23 0.203661 0.069538 81 22 1 5.808 NxAQ ChHH 32.7 11.2 137.8 6.713106 2.7429e−11 0.2373 0.081146 31 35 24 15.55 YxxxxE CcchhH 85.7 29.3 538.1 10.71176 1.2450e−26 0.159264 0.054469 95 106 83 21.141 DxxxxV EccccE 29.2 10 277.5 6.186242 8.4465e−10 0.105225 0.036023 30 33 29 5.592 DxxxxW CccccE 33.5 11.5 263 6.65024 4.0350e−11 0.127376 0.04362 42 41 36 8.248 DSxE CChH 66 22.6 239.7 9.582583 1.3711e−21 0.275344 0.094387 64 81 50 13.344 GxNxxE CcChhH 35.9 12.3 268.7 6.879201 8.2900e−12 0.133606 0.045839 38 44 32 11.001 SQxxT HHhhH 29.8 10.2 148.5 6.344138 3.1629e−10 0.200673 0.068853 30 38 22 5.454 RxxxxI HhhccC 47.6 16.3 347.7 7.919529 3.2760e−15 0.1369 0.047007 56 60 52 10.429 SPG ECC 28.7 9.9 160 6.179461 8.9798e−10 0.179375 0.061769 33 34 23 10.241 DxxxxT EccccE 70.6 24.4 581 9.569481 1.4539e−21 0.121515 0.041937 79 88 58 9.906 YxxxxQ HhhhcC 40.4 14 300.9 7.244583 5.9055e−13 0.134264 0.046407 52 56 48 10.814 ExSG HhHC 34 11.8 154.5 6.751139 2.0640e−11 0.220065 0.076071 35 44 32 6.005 SSTK HCEE 54.6 18.9 198.1 8.640682 7.9973e−18 0.275618 0.09533 65 27 1 5.536 RxxxxY CcchhH 31.1 10.8 222.8 6.349861 2.9387e−10 0.139587 0.048342 40 43 32 1.884 WxxxQ HhhhH 201.9 69.9 1001.1 16.36292 4.8607e−60 0.201678 0.069854 204 248 166 40.546 DxAxxR ChHhhH 33.9 11.7 212.5 6.651301 3.9842e−11 0.159529 0.055269 39 46 35 7 YQxxL HHhhH 40.1 13.9 386.6 7.155977 1.1141e−12 0.103725 0.035961 45 45 40 8.875 YxxxxR EecccC 35.9 12.5 301.6 6.782838 1.5881e−11 0.119032 0.041308 39 45 28 4.289 RxxGxP HhhCcC 35 12.1 274.9 6.707417 2.6783e−11 0.127319 0.044184 47 44 39 11.283 VSxxE CChhH 56.4 19.6 340.2 8.573591 1.3696e−17 0.165785 0.057539 61 73 52 5.783 SxxKxD HceEeE 57 19.8 313.1 8.642784 7.5321e−18 0.18205 0.063201 72 20 1 9.833 RxxGA HhcCC 31.8 11 222.8 6.40728 2.0139e−10 0.142729 0.049563 38 42 35 6.731 NxKxD CeEeE 36.1 12.5 155.1 6.939188 5.5327e−12 0.232753 0.080856 43 14 2 6.641 PTE CCH 41.7 14.5 177.9 7.44701 1.3352e−13 0.234401 0.081576 44 40 20 7.061 TLP HCC 29.6 10.3 120.5 6.286176 4.5831e−10 0.245643 0.085508 34 39 27 9 DxxGxG CccCcC 95.4 33.3 1003.2 10.95388 8.3945e−28 0.095096 0.033166 90 100 43 17.791 RxGL HhCC 42.9 15 220.2 7.477473 1.0395e−13 0.194823 0.067983 49 51 45 5.1 KxxGxN HhhCcC 32.1 11.2 196.9 6.425281 1.7880e−10 0.163027 0.056929 39 43 25 4.915 QxxND HhhHH 36.3 12.7 151.8 6.922566 6.1794e−12 0.23913 0.083607 38 44 30 3.862 TPN CHH 40.3 14.1 123 7.419598 1.6934e−13 0.327642 0.114566 39 37 12 19.754 PxxxxH CcchhH 41.9 14.7 291.5 7.302953 3.7793e−13 0.143739 0.050274 48 49 40 12.086 NxxRR HhhHH 32.6 11.4 160.5 6.512143 1.0185e−10 0.203115 0.071054 35 40 32 12.332 DVQ CHH 29.6 10.4 118.8 6.257869 5.4630e−10 0.249158 0.087188 33 38 20 6.179 ExxGxP HhcCcC 32.8 11.5 226.1 6.450292 1.4987e−10 0.145069 0.050838 39 40 36 2.2 QAxG HHcC 58.1 20.4 220.9 8.766703 2.5643e−18 0.263015 0.092292 61 73 51 12.929 PExxN HHhhH 42.6 15 197.4 7.430722 1.4792e−13 0.215805 0.075812 45 51 39 6.752 TxxSR HhhHH 30.7 10.8 166.3 6.270388 4.8902e−10 0.184606 0.064858 32 34 26 6.98 NxxxV HhhcC 46.4 16.3 193.8 7.784519 9.6539e−15 0.239422 0.084169 52 56 46 6.751 SxxVS HhhHH 38.1 13.4 307.2 6.902395 6.7722e−12 0.124023 0.043603 43 44 32 4.586 IxxxxQ CchhhH 31.2 11 289.5 6.22516 6.3449e−10 0.107772 0.037904 33 37 29 4.5 WxxxR HhhhC 44.2 15.5 224 7.531965 6.7825e−14 0.197321 0.069416 55 55 38 5.651 TxVxK EeEeE 106.2 37.4 568.5 11.64047 3.4471e−31 0.186807 0.065781 120 42 7 11.641 GDxT CCcE 34.9 12.3 154.9 6.715037 2.5763e−11 0.225307 0.079419 35 31 19 11.5 SAxG HHhC 37.8 13.3 158.5 7.005915 3.3764e−12 0.238486 0.084068 42 42 30 6.643 MxxxxK CchhhH 41.1 14.5 281.9 7.178243 9.3821e−13 0.145796 0.051396 46 53 43 11.993 PAxxS HHhhH 35.4 12.5 225.7 6.664198 3.5462e−11 0.156845 0.055384 41 45 31 3.833 SxAxxE ChHhhH 40.7 14.4 301.5 7.112073 1.5082e−12 0.134992 0.047697 47 50 44 4.828 AxxAS HhhHC 33 11.7 230 6.390864 2.1762e−10 0.143478 0.050877 40 43 31 3.792 QxxSR HhhHH 37.1 13.2 179.3 6.839369 1.0685e−11 0.206916 0.073569 34 35 29 6.433 KPxY CCcC 42.7 15.2 188.2 7.350314 2.6651e−13 0.226886 0.080837 37 50 23 4.761 QxxN HchH 38.1 13.6 85 7.25218 6.0503e−13 0.448235 0.159919 35 34 7 10.112 YxxxxR HhhccC 40.1 14.3 271.5 6.994423 3.4742e−12 0.147698 0.052783 45 53 41 9.85 DxxxNG CcccCC 41.8 14.9 391.2 7.084546 1.7924e−12 0.106851 0.038196 40 42 19 10.25 GxTxxD CcChhH 47.3 16.9 366.4 7.557245 5.3153e−14 0.129094 0.046209 55 63 38 13.246 RxxxxY HhhccC 47.4 17 288.6 7.611015 3.5521e−14 0.164241 0.058825 55 57 40 15.183 FxxxxA CcchhH 40.1 14.4 430 6.904445 6.4267e−12 0.093256 0.033416 48 45 35 5.002 NxxNA HhhHH 36.5 13.1 245.9 6.651858 3.7623e−11 0.148434 0.053217 33 37 22 4.333 RxxGV EccCC 36.3 13 227.8 6.632045 4.3072e−11 0.15935 0.057259 41 43 9 2.271 GxxxxY CchhhH 50.8 18.3 530.6 7.746419 1.1980e−14 0.095741 0.034427 57 64 39 23.548 KxxGxP HhhCcC 39.7 14.3 276 6.907485 6.3677e−12 0.143841 0.051742 48 51 38 7.563 DxxFA HhhHH 32.1 11.6 269 6.179608 8.2368e−10 0.119331 0.042945 33 37 33 4.083 IxxxxQ CcchhH 42 15.1 342 7.070283 1.9778e−12 0.122807 0.044214 39 45 26 4.92 PGxxE CChhH 48.5 17.5 230.5 7.72459 1.4791e−14 0.210412 0.07577 48 56 43 11.467 KVDK EEEE 99.7 35.9 374.1 11.1934 5.8880e−29 0.266506 0.096012 109 34 1 10.641 TxxxxY CcchhH 36.8 13.3 315.3 6.590914 5.5645e−11 0.116714 0.042141 47 47 37 7.79 KxxxxY CcchhH 48.4 17.5 296.3 7.622571 3.2081e−14 0.163348 0.059004 51 54 40 23.023 DxP EhH 32.2 11.6 75.8 6.55045 8.2319e−11 0.424802 0.153554 35 30 13 3.667 DxxE EhhH 85.6 30.9 287.7 10.39894 3.3866e−25 0.297532 0.107574 93 100 54 25.308 AAxxG HHhhC 61.5 22.3 619.8 8.471116 3.0525e−17 0.099226 0.035912 73 79 69 15.583 SFT EEE 35.9 13 322.2 6.484796 1.1250e−10 0.111421 0.04034 43 44 40 4.286 PExxT HHhhH 42.2 15.3 228.7 7.116551 1.4320e−12 0.184521 0.066926 48 42 28 6.5 SxTxxD HcEeeE 58.2 21.1 334.4 8.334126 1.0029e−16 0.174043 0.063172 74 20 1 10.833 YxxxQ HhhhC 102 37.1 412.9 11.16651 7.8027e−29 0.247033 0.089869 111 130 98 26.582 KxxGxD HhcCcC 46.7 17 284.7 7.415308 1.5458e−13 0.164032 0.059814 58 56 37 7.429 GLxP CCcH 48.9 17.8 319.3 7.570949 4.6990e−14 0.153148 0.055852 54 59 47 11.95 GxxxxQ CchhhH 65.4 23.9 462.5 8.714553 3.6676e−18 0.141405 0.05169 66 77 57 10.766 STA CHH 36.2 13.2 133.8 6.648716 3.9121e−11 0.270553 0.098935 39 40 33 3.125 TKVD EEEE 98.5 36 385.6 10.93326 1.0444e−27 0.255446 0.093416 111 34 2 11.641 IxxxQ CchhH 160.4 58.7 884.1 13.74543 6.8834e−43 0.181427 0.06636 158 176 113 39.776 VxxxxE EcchhH 59.9 21.9 499.1 8.298175 1.3176e−16 0.120016 0.04391 66 80 34 11.21 KSR CCH 35.5 13 108.5 6.655961 3.8052e−11 0.327189 0.119737 38 31 11 7.78 YxxxT HhhhC 53.2 19.5 299.7 7.889466 3.8511e−15 0.177511 0.06509 57 61 45 12.654 DRxG HHhC 37.3 13.7 145.5 6.710008 2.5502e−11 0.256357 0.094011 42 48 40 5.333 HxxxxP HhhccC 39.5 14.5 244.4 6.775202 1.5709e−11 0.16162 0.059279 39 40 31 10.047 MxxxxE HhhccC 34.2 12.5 291.7 6.249721 5.1266e−10 0.117244 0.043007 42 44 34 6.241 CxxxN HhhhC 35 12.8 213.2 6.379588 2.2496e−10 0.164165 0.060223 37 37 21 10.833 ERxG HHcC 76.1 28 265.7 9.603856 1.0100e−21 0.286413 0.105454 79 91 68 16.416 LxxxE EehhH 67.4 24.8 495.9 8.759329 2.4343e−18 0.135914 0.050103 75 77 37 7.941 NSG ECC 33.8 12.5 139.3 6.33532 3.0683e−10 0.242642 0.08945 41 36 13 7.933 GxTxY CcEeE 52.6 19.4 391 7.732901 1.3037e−14 0.134527 0.04961 58 58 25 16.729 TxxxxQ CchhhH 45.5 16.8 336.6 7.185919 8.2803e−13 0.135175 0.049896 53 63 45 9.89 KxxxxY HhhccC 67 24.7 384 8.786447 1.9357e−18 0.174479 0.06441 78 85 65 16.036 WxxxH HhhhH 68.2 25.2 453.8 8.807377 1.5890e−18 0.150286 0.055571 76 85 68 19.873 FxxxxE CcchhH 87.8 32.5 685.4 9.926259 3.9216e−23 0.1281 0.047474 108 119 97 22.741 DxSV CcCE 35.2 13.1 239.4 6.298075 3.7348e−10 0.147034 0.054574 33 39 26 9.027 GxDxxE CcChhH 36.8 13.7 254.3 6.426476 1.6131e−10 0.144711 0.053792 41 45 34 3.92 ExxGI HhcCC 36.6 13.7 252.1 6.381846 2.1498e−10 0.14518 0.054187 44 50 41 4.904 YxxxM HhhhH 172.2 64.3 1625.2 13.71903 9.3692e−43 0.105956 0.039595 187 196 139 41.857 ExLP HhCC 42.2 15.8 295.8 6.839588 9.7186e−12 0.142664 0.053319 48 51 43 7 LxxxxV CchhhH 90.3 33.8 1719.7 9.813784 1.1574e−22 0.052509 0.019657 106 108 80 33.523 YxxxH HhhhH 163.9 61.4 985.3 13.51545 1.5489e−41 0.166345 0.062287 185 210 154 53.189 STxxR HHhhH 44.8 16.8 265.4 7.06881 1.9236e−12 0.168802 0.063213 46 43 30 13.239 TxVxxK EeEeeE 70.3 26.3 562.7 8.776302 2.0407e−18 0.124933 0.046795 81 18 2 6.808 KxSxxE CcChhH 34.8 13 249.7 6.189193 7.3797e−10 0.139367 0.052226 42 44 35 8.25 QxxxxI HhhhcC 36.6 13.7 262.5 6.340297 2.7931e−10 0.139429 0.052303 42 50 28 6.99 RSxxL HHhhH 42.8 16.1 361.8 6.827799 1.0410e−11 0.118297 0.044377 43 45 33 3.5 WxxxN HhhhH 162.9 61.2 825.6 13.50641 1.7623e−41 0.197311 0.074149 156 193 123 36.661 DxAxxE ChHhhH 48.7 18.3 339.8 7.304968 3.3650e−13 0.14332 0.053861 55 65 51 9.053 CxxxN HhhhH 40.5 15.2 374.6 6.602715 4.8363e−11 0.108115 0.040704 40 42 34 8.099 LIS EEE 36 13.6 561.3 6.168581 8.1408e−10 0.064137 0.024159 42 25 20 6.364 LSxG HHcC 39.7 15 242.9 6.598851 5.0502e−11 0.163442 0.061625 46 50 39 4.151 LSxxQ CChhH 60.8 22.9 428.9 8.130612 5.1480e−16 0.141758 0.053451 72 77 56 10.682 YRG ECC 44.6 16.9 163.1 7.137134 1.2043e−12 0.273452 0.103338 54 50 22 6.727 NTKV CEEE 38 14.4 156.3 6.545601 7.4133e−11 0.243122 0.091884 43 15 2 6.808 AQxxS HHhhH 50.4 19 360.1 7.381135 1.8871e−13 0.139961 0.052899 54 62 43 15.095 ISxxE CChhH 45.1 17.1 314.7 6.975012 3.6776e−12 0.143311 0.05425 52 57 50 6.747 SSxxxD HCeeeE 41.2 15.6 216.6 6.724105 2.1591e−11 0.190212 0.072065 54 15 1 6.5 RxxGL HhhCC 41.8 15.9 247.8 6.726746 2.0975e−11 0.168684 0.064055 53 59 49 11.51 HxxxW HhhhH 45.1 17.1 463.5 6.884276 6.8432e−12 0.097303 0.036968 53 60 47 13.411 KxxxxN CchhhH 38.6 14.7 224.6 6.463752 1.2361e−10 0.171861 0.065304 42 41 22 10.588 KxxxxQ CcchhH 80.6 30.6 502.4 9.316053 1.4468e−20 0.16043 0.060976 85 89 65 15.642 IxxxY CchhH 38.1 14.5 319.7 6.350739 2.5454e−10 0.119174 0.045305 45 45 34 18.265 YxxxL HhhhC 91.7 34.9 677.5 9.880421 6.0041e−23 0.135351 0.051474 107 115 93 33.564 DAxG HHhC 38.6 14.7 177.7 6.514124 8.9759e−11 0.21722 0.082658 44 52 39 10.682 NxxxxR CchhhH 74.6 28.5 442.8 8.941105 4.6087e−19 0.168473 0.064272 80 92 66 13.163 LSA CCH 54 20.6 304.8 7.618303 3.0894e−14 0.177165 0.067607 58 69 47 8.75 AxxRH HhhHH 52.1 19.9 294.8 7.480402 8.9042e−14 0.17673 0.067458 52 53 27 9.9 EGxP HCcC 36.9 14.1 148.4 6.390062 2.0520e−10 0.248652 0.094911 41 41 17 8.331 AFG HHC 43 16.4 221.9 6.81187 1.1651e−11 0.193781 0.074044 50 59 42 3.041 STK CEE 101.6 38.9 261.2 10.9062 1.3949e−27 0.388974 0.148807 104 57 4 8.703 ExxxSK HhhhHH 43.5 16.6 292.1 6.778914 1.4388e−11 0.148922 0.05698 52 56 39 9.048 GxDxxA CcChhH 41.7 16 346.5 6.586367 5.2939e−11 0.120346 0.046127 46 50 31 10.654 FxxxQ CchhH 79.8 30.6 582.3 9.138367 7.4489e−20 0.137043 0.052546 91 90 68 7.139 GxSxxD CcChhH 52 19.9 441.1 7.34755 2.3629e−13 0.117887 0.045205 63 68 51 14.451 SVY EEE 38.3 14.7 601.1 6.238409 5.0979e−10 0.063717 0.024433 45 33 14 9.333 SxxxH HhhhH 315.2 120.9 1433.7 18.46693 4.5899e−76 0.219851 0.084326 284 367 224 65.875 RRxG HHhC 58 22.3 215.4 7.997367 1.5668e−15 0.269266 0.103372 60 66 53 11.393 YxxxI HhhhC 40 15.4 401.6 6.397141 1.8383e−10 0.099602 0.038321 51 50 43 12.339 IxxS EccE 49.9 19.2 334.1 7.209842 6.5925e−13 0.149356 0.057518 58 50 6 5.361 RxxGL HhcCC 53.5 20.6 336 7.465023 9.8050e−14 0.159226 0.061435 64 73 61 6.592 NxxxQ HhhhC 82.6 31.9 264.1 9.579875 1.2068e−21 0.31276 0.12071 96 106 83 10.611 KxHG HhCC 42.9 16.6 163.8 6.820623 1.1077e−11 0.261905 0.101187 46 45 31 4.473 WxxxY HhhhH 104.8 40.6 939.3 10.30613 7.5914e−25 0.111572 0.043203 108 124 78 32.422 YxxxxQ EecccC 38.3 14.8 329 6.232553 5.3126e−10 0.116413 0.045103 38 44 35 7.961 RxxxxQ CchhhH 39 15.1 262 6.321392 3.0279e−10 0.148855 0.057753 45 46 40 12.704 RxxxxV HhhccC 60.7 23.6 427.7 7.873856 3.9908e−15 0.141922 0.05507 76 75 62 13.656 MxxxR HhhhC 53.5 20.8 301.5 7.445446 1.1360e−13 0.177446 0.068865 68 58 36 10.359 QRG HCC 49.4 19.2 147.2 7.401983 1.6748e−13 0.335598 0.130253 53 54 39 8.2 SxxAA HhhHH 78.9 30.6 960.7 8.862496 8.8792e−19 0.082128 0.031889 88 93 83 16.082 MxxxE CchhH 292 113.4 1275.4 17.56392 5.5301e−69 0.228948 0.088946 304 324 216 51.442 LxxxQ CchhH 328 127.5 1903.8 18.38234 2.1159e−75 0.172287 0.066973 351 403 271 51.12 RxxxD ChhhH 36.4 14.2 125.1 6.27883 4.1861e−10 0.290967 0.113143 37 45 33 6.167 SSxxS HHhhH 45 17.5 264.2 6.803607 1.1954e−11 0.170326 0.066232 52 51 32 6.945 FxxxQ HhhhH 322.3 125.4 2057.5 18.15157 1.4421e−73 0.156646 0.060927 325 351 248 84.147 QTxxA HHhhH 38.6 15 285.6 6.251316 4.7151e−10 0.135154 0.052588 40 45 31 10.029 PxN EhH 40.1 15.6 159.8 6.523918 8.2562e−11 0.250939 0.097705 43 47 28 14.533 LxxxxL CchhhH 154.3 60.1 2989.1 12.26441 1.5679e−34 0.051621 0.020122 172 187 154 49.359 LxxGA HhcCC 40.9 16 451.2 6.360487 2.2876e−10 0.090647 0.035351 56 60 43 3.567 HPY CCC 40.1 15.6 184.8 6.46315 1.2178e−10 0.216991 0.084649 36 41 21 8.774 AxxxxY CcchhH 41.9 16.4 400.6 6.451277 1.2660e−10 0.104593 0.040817 45 47 29 12.417 KxTG HhHC 76.9 30 329 8.978773 3.2532e−19 0.233739 0.091216 89 88 60 7.166 SPxxxS ECceeE 38.1 14.9 211.2 6.24142 5.0762e−10 0.180398 0.070475 43 28 3 2 STxxD CEeeE 70.3 27.5 272.3 8.618319 8.1370e−18 0.258171 0.100879 78 26 4 8.333 ESxG HHhC 37.3 14.6 152.8 6.251437 4.8643e−10 0.24411 0.095485 44 53 35 5.47 KRG HHC 39.6 15.5 122.7 6.553035 6.9434e−11 0.322738 0.126252 42 45 40 3 LxxxxE CchhhH 64.6 25.3 535.1 8.003582 1.3751e−15 0.120725 0.047287 73 76 64 16.419 NxxP HhcH 58.9 23.1 169.6 8.014526 1.3658e−15 0.347288 0.136201 57 64 28 17.097 WC CC 77.2 30.3 378.1 8.889715 7.1536e−19 0.204179 0.080088 74 86 41 16.678 DxAxxA ChHhhH 40.7 16 424.8 6.30617 3.2326e−10 0.09581 0.037604 47 50 43 5.173 EGI HCC 38 14.9 170.6 6.252963 4.7535e−10 0.222743 0.087481 40 46 21 7.513 ExxxxK EecceE 49.3 19.4 237 7.097573 1.4863e−12 0.208017 0.081721 53 70 45 9.907 GxxxxS CcchhH 154.1 60.6 1208.3 12.32969 7.0867e−35 0.127535 0.050132 163 180 118 70.731 SxTxV HcEeE 67.5 26.5 339.7 8.277657 1.4600e−16 0.198705 0.078155 84 28 1 10.869 GxxxxN CcchhH 104.6 41.2 673.7 10.20739 2.0976e−24 0.155262 0.061083 120 141 79 47.325 TxxxKK EeeeEE 69.9 27.5 416.3 8.363251 7.0078e−17 0.167908 0.066081 80 17 1 6.808 YxY CcE 84.9 33.4 504.5 9.207153 3.8374e−20 0.168285 0.066298 89 100 48 20.439 SxAE ChHH 122.9 48.4 589.8 11.16867 6.7314e−29 0.208376 0.082117 133 148 101 18.512 ExGF HcCC 39.4 15.5 239.4 6.259081 4.4518e−10 0.164578 0.064913 53 52 40 6.293 LTS CCH 43 17 240.7 6.558201 6.2855e−11 0.178646 0.070463 44 41 21 2.257 NDG ECC 41.8 16.5 146.6 6.601243 4.8788e−11 0.28513 0.112713 43 47 12 10.913 NxxxxF CccccE 47.6 18.8 542.3 6.750994 1.6369e−11 0.087774 0.03471 49 51 33 10.371 PxxxxQ CchhhH 62.2 24.6 503.6 7.77407 8.5531e−15 0.123511 0.048843 74 81 67 12.837 RxxxR HhhhC 188.3 74.5 575 14.13525 2.7770e−45 0.327478 0.129536 207 244 169 47.934 DxAS ChHH 45.9 18.2 275.4 6.736084 1.8618e−11 0.166667 0.065934 46 55 42 3.25 QSP EEC 55.5 22 358.1 7.386743 1.7114e−13 0.154985 0.061328 68 47 8 3.5 RRxG HHcC 56.3 22.3 211.9 7.619259 3.0185e−14 0.265691 0.105141 57 66 51 12.853 LPP CCH 51 20.2 286.8 7.109054 1.3390e−12 0.177824 0.070421 54 62 44 8.701 SxxxxD CchhhH 41.5 16.5 299.4 6.349576 2.4419e−10 0.138611 0.054971 42 50 31 10.8 NxxxxN HhhccC 60 23.8 376.7 7.661546 2.0833e−14 0.159278 0.063216 70 77 64 7.58 NAxxS HHhhH 38.9 15.4 268.6 6.149912 8.7835e−10 0.144825 0.057482 38 39 20 3.817 RxTG HhHC 45.1 17.9 213.7 6.711082 2.2341e−11 0.211044 0.083822 52 59 49 3.924 YxxxF HhhhH 151.3 60.1 2015.5 11.93721 8.2988e−33 0.075068 0.029833 153 168 122 51.948 VGS ECC 50.8 20.2 338.6 7.014581 2.6019e−12 0.15003 0.059706 52 58 33 16.101 IxxxxI CchhhH 43.8 17.4 992.1 6.369436 2.0703e−10 0.044149 0.017576 52 56 48 7.959 SxxVD CeeEE 71.1 28.4 311.2 8.413504 4.5859e−17 0.22847 0.091179 78 27 5 8 GxxAA HhhHH 53.5 21.4 1130 7.01614 2.4760e−12 0.047345 0.018914 58 70 55 17.258 MxxxH HhhhH 93 37.2 734.8 9.400986 5.9947e−21 0.126565 0.050572 95 118 85 36.595 PxDQ ChHH 43.8 17.5 180.6 6.602266 4.6907e−11 0.242525 0.097075 51 57 29 7.011 CG CH 66.5 26.7 303.6 8.076594 7.6058e−16 0.219038 0.087834 69 78 41 14.932 SxxxVD HceeEE 58.7 23.5 333.5 7.513806 6.4629e−14 0.176012 0.070611 74 20 1 9.833 AxxGL HhcCC 49.9 20 437.5 6.834044 9.1072e−12 0.114057 0.045773 74 75 65 10.817 SSxK HCeE 57.9 23.2 198.2 7.653307 2.2980e−14 0.292129 0.117242 69 32 1 5.536 ExGG EeCC 45.4 18.2 306.7 6.559515 6.0218e−11 0.148027 0.059455 44 49 22 6 IxxxxL CchhhH 79.6 32.1 1654.6 8.474998 2.5182e−17 0.048108 0.019383 92 98 78 19.491 FPxR CCcC 41.6 16.8 246.4 6.282883 3.7211e−10 0.168831 0.06804 44 37 27 15.541 KxDxK EeEeE 78.2 31.5 395.3 8.663783 5.1313e−18 0.197824 0.079765 86 28 3 8.808 AxxxxQ CchhhH 57.6 23.3 448.3 7.308742 2.9604e−13 0.128485 0.051908 61 82 40 11.14 VxxxxR CchhhH 75.7 30.6 650.5 8.356763 7.0348e−17 0.116372 0.047016 96 101 80 14.641 AxGL HcCC 79.5 32.1 539.5 8.617327 7.5507e−18 0.147359 0.059556 99 101 90 14.846 EFG HHC 47.2 19.1 189.4 6.788653 1.2971e−11 0.249208 0.100739 55 59 41 16.85 LxxxxQ CcchhH 58.5 23.7 469.2 7.336592 2.3940e−13 0.12468 0.050508 68 72 61 11.976 RSxG HHcC 54.3 22 224.4 7.250022 4.7424e−13 0.241979 0.098051 60 66 47 6.848 YxxxxS HhhhcC 44.5 18 410.7 6.372091 2.0302e−10 0.108352 0.04392 56 56 45 12.558 AxxAA HhhHC 61.6 25 435.1 7.54746 4.8688e−14 0.141577 0.057408 79 83 77 14.553 YxxxN HhhhC 131.6 53.4 626.1 11.19454 4.8487e−29 0.21019 0.085253 138 164 107 10.14 NExxR HHhhH 68.6 27.9 378.6 7.9956 1.4251e−15 0.181194 0.073776 74 84 53 12.711 YxxxY HhhhH 208.5 84.9 1723.4 13.75447 5.1591e−43 0.120982 0.049272 217 240 173 68.563 TxxxR HhhhC 81.7 33.3 353.9 8.818101 1.3071e−18 0.230856 0.094038 93 98 74 13.874 RxxxxE HhhccC 173.9 70.9 874 12.7612 2.9847e−37 0.19897 0.08112 195 205 162 32.84 LxxxV CchhH 94.4 38.5 929.9 9.198796 3.8794e−20 0.101516 0.041413 93 96 68 17.959 RExG HHhC 92.3 37.7 353.8 9.41839 5.1848e−21 0.260882 0.106451 103 113 87 24.407 VxxxxQ CcchhH 56.1 22.9 488.3 7.10183 1.3279e−12 0.114888 0.046923 78 85 68 8.301 ExxGL HhcCC 64.7 26.4 437.9 7.674219 1.8107e−14 0.147751 0.060392 82 83 73 10.513 TPxxxK CHhhhH 42.6 17.4 322 6.202797 6.0232e−10 0.132298 0.054102 49 49 34 12.211 RxxxF HhhhC 42.6 17.4 230.1 6.267413 4.0522e−10 0.185137 0.075788 43 51 42 5.093 RxxQ ChhH 123 50.4 388.2 10.96953 6.1545e−28 0.316847 0.129758 136 158 98 25.056 FxxxQ HhhhC 50.5 20.7 311.9 6.783616 1.2804e−11 0.161911 0.066325 63 69 53 10.301 KDxG HHhC 61.6 25.2 236 7.660531 2.0910e−14 0.261017 0.106924 64 75 50 10.466 YxxxR HhhhH 507.5 207.9 2808.6 21.59003  2.4287e−103 0.180695 0.074032 523 598 413 103.922 WxxxR HhhhH 205.3 84.2 1244.6 13.6702 1.6585e−42 0.164953 0.067642 211 254 169 61.82 KxFG HhHC 43.8 18 249.9 6.320153 2.8637e−10 0.17527 0.071956 55 60 51 10.832 KxxGV HhhCC 49.3 20.3 325.6 6.663139 2.9074e−11 0.151413 0.062217 63 66 54 13.445 QKxG HHhC 50.3 20.7 190.7 6.89803 5.9432e−12 0.263765 0.108445 58 60 48 8.676 GxxxxR CchhhH 118.7 48.8 850.2 10.29793 7.7223e−25 0.139614 0.057438 126 137 107 23 QExG HHhC 44.7 18.4 194.8 6.446972 1.2707e−10 0.229466 0.094406 55 52 44 11.216 NxxxxK CchhhH 81.3 33.5 456 8.591494 9.3418e−18 0.178289 0.073378 93 109 78 16.967 FxxxN HhhhH 179.4 73.9 1396.3 12.61498 1.8611e−36 0.128482 0.05291 198 228 158 40.24 AxxQS HhhHH 45.5 18.8 322.8 6.35022 2.3121e−10 0.140954 0.058203 52 53 48 10.166 TEA CHH 96 39.7 292.4 9.607131 8.5115e−22 0.328317 0.13583 92 114 61 11.498 YxxxT EcccE 41.1 17 171.8 6.153075 8.4367e−10 0.239232 0.099017 47 53 13 6.453 TKxxK EEeeE 96 39.8 398.3 9.392073 6.4809e−21 0.241024 0.099903 109 33 4 11.141 AxxAA HhhHH 232.6 96.4 3380.2 14.07095 5.9399e−45 0.068812 0.028524 260 292 237 37.003 ExxxF HhhhC 51.9 21.5 296.5 6.797281 1.1516e−11 0.175042 0.072608 60 71 51 13.323 LSxxE CChhH 117.4 48.7 851.8 10.13758 3.9929e−24 0.137826 0.057178 131 149 113 25.064 SAA CHH 97.7 40.5 376.8 9.504205 2.2325e−21 0.259289 0.10758 104 111 64 12.337 DxxxxQ CchhhH 68.3 28.3 458.4 7.749134 9.8809e−15 0.148997 0.061827 79 86 64 16.775 EAxxxQ HHhhhH 45.2 18.8 422.8 6.237266 4.7014e−10 0.106906 0.044414 47 52 42 11.095 FxN ChH 67.5 28 272.3 7.865817 4.0460e−15 0.247888 0.103 67 74 34 17.384 TxNG EeCC 49.7 20.7 275.2 6.622482 3.8018e−11 0.180596 0.075273 51 58 42 8.901 HxxxQ HhhhH 327.4 136.5 1404.3 17.19861 2.9556e−66 0.233141 0.097192 328 400 272 59.385 HxxxN HhhhH 195.7 81.6 841.4 13.28816 2.9476e−40 0.232589 0.097006 204 230 159 45.887 NxxxR HhhhH 648.3 270.4 2518.1 24.32263  1.2367e−130 0.257456 0.107389 610 743 462 158.253 NGI CCE 49.4 20.6 260.4 6.597702 4.4957e−11 0.189708 0.079259 53 51 42 13.4 DKxG HHhC 59.5 24.9 228.9 7.356353 2.0816e−13 0.259939 0.108634 67 74 39 13.515 SxxxxY ChhhhH 66 27.6 674.7 7.466487 8.5770e−14 0.097821 0.040894 75 86 69 24.58 DAxxR CHhhH 47.2 19.7 267.6 6.420888 1.4506e−10 0.176383 0.073777 49 43 20 16.283 HxxxY HhhhH 136.7 57.2 1013.4 10.82597 2.7198e−27 0.134892 0.056424 146 162 94 52.442 SxTK HcEE 87.3 36.5 320.2 8.926379 4.8515e−19 0.272642 0.114065 104 44 2 10.869 RxxxF HhccC 95.2 40 501.8 9.091054 1.0429e−19 0.189717 0.079765 107 113 90 32.509 SxxAQ HhhHH 48.8 20.5 367.6 6.420944 1.4190e−10 0.132753 0.05585 54 59 41 8.195 EGG ECC 45.7 19.2 174.1 6.394959 1.7583e−10 0.262493 0.110529 50 56 38 7.878 LxxxxY HhhccC 53.2 22.4 957.7 6.577507 4.8789e−11 0.05555 0.023412 58 53 45 13.611 ExTG HhHC 52.2 22 309.4 6.677412 2.5699e−11 0.168714 0.071133 61 72 54 7.579 STxV CEeE 79.7 33.6 368.4 8.33438 8.3322e−17 0.216341 0.091281 88 33 6 6.767 GxxxL ChhhC 45.7 19.3 438.5 6.14382 8.3292e−10 0.104219 0.044027 54 50 31 5.267 PxxAA HhhHH 66 27.9 816.2 7.342254 2.1476e−13 0.080863 0.034173 74 82 64 11.664 YxxxQ HhhhH 376.9 159.4 2150.4 17.90893 1.0512e−71 0.17527 0.074107 374 436 305 111.215 DxxxxR CchhhH 136.7 58 811.5 10.71836 8.6960e−27 0.168453 0.071505 143 168 128 34.131 HxH ChH 49.4 21 166.4 6.637432 3.4999e−11 0.296875 0.126078 48 58 40 14.723 PxxxxQ CcchhH 109.4 46.5 1083.7 9.42162 4.5216e−21 0.10095 0.042935 118 135 95 24.269 SxExxR ChHhhH 62.2 26.5 481.7 7.130862 1.0256e−12 0.129126 0.055033 80 87 70 14.016 SGxxxD EEeccE 50.1 21.4 292.4 6.4458 1.1982e−10 0.171341 0.073174 60 62 3 2 AxxAS HhhHH 77.3 33.1 862.3 7.834917 4.7308e−15 0.089644 0.038384 98 95 79 12.6 AxxRR HhhHH 119 51 722.4 9.873794 5.5640e−23 0.164729 0.070617 129 147 115 15.089 NxxxxE CcchhH 188.1 80.7 1090.7 12.43087 1.8292e−35 0.172458 0.073955 206 216 153 32.263 RKxG HHhC 59.6 25.6 254 7.09804 1.3380e−12 0.234646 0.10065 67 79 54 6.282 RxxxxE CchhhH 60.4 25.9 383.1 7.017736 2.3228e−12 0.157661 0.067628 75 91 59 8.743 LxxxxV HhhccC 66.2 28.4 1605.3 7.15494 8.3081e−13 0.041238 0.017695 82 92 77 17.354 WxxxE HhhhH 212.2 91.1 1285.6 13.16755 1.3835e−39 0.165059 0.07084 221 251 188 46.713 QxxxM HhhhH 782.6 336.4 3046.6 25.79586  1.0406e−146 0.256877 0.110409 762 926 577 115.112 YxxxxD HhhccC 49.9 21.5 413.3 6.306176 2.9083e−10 0.120736 0.051916 58 62 47 19.646 PxW ChH 79.8 34.3 415 8.106427 5.4043e−16 0.192289 0.082693 81 103 66 17.843 AxxQD HhhHH 65.9 28.4 324.1 7.377042 1.6844e−13 0.203332 0.087528 67 71 29 16.326 WPS CCC 53.8 23.2 328.9 6.603471 4.1321e−11 0.163576 0.070417 57 62 15 16.457 QxxxR HhhhC 139 60 517.3 10.84212 2.2965e−27 0.268703 0.116033 151 185 120 21.397 QxxxxL HhhhcC 57.2 24.7 531.5 6.693205 2.1962e−11 0.10762 0.046493 73 74 64 14.227 PxxxN HhhhC 62.1 26.8 260.8 7.184689 7.0636e−13 0.238113 0.102927 59 74 51 15.003 GxTxxE CcChhH 54.9 23.8 506.5 6.54652 5.9175e−11 0.108391 0.046894 65 71 59 5 AxxRD HhhHH 77.3 33.4 420.4 7.9035 2.7836e−15 0.183873 0.07956 91 98 81 17.109 IxxxxE CcchhH 74.6 32.3 754.4 7.611808 2.7000e−14 0.098887 0.042796 93 95 87 13.777 LTxxE CChhH 100.6 43.5 866 8.87308 7.1316e−19 0.116166 0.050279 114 121 90 17.283 DxxRR HhhHH 121.9 52.8 600.5 9.963409 2.2695e−23 0.202998 0.087883 141 150 131 22.814 RAxxxR HHhhhH 62.9 27.3 536.8 6.997202 2.6193e−12 0.117176 0.050836 68 75 64 10.493 ExFG HhHC 57 24.7 365.9 6.717061 1.8836e−11 0.15578 0.067613 73 82 64 7.303 HxxR HhcC 76.9 33.4 263.5 8.056204 8.3542e−16 0.291841 0.126735 84 94 67 23.162 ExxxY HhhhC 61.4 26.7 310.7 7.030848 2.1101e−12 0.197618 0.085867 71 83 64 13.696 SxQE ChHH 54.8 23.8 271.3 6.647848 3.0642e−11 0.20199 0.08778 65 72 58 10.729 GxxxxR CcchhH 133.1 57.9 856.2 10.24474 1.2603e−24 0.155454 0.067572 154 174 129 29.99 KxxW CchH 52.9 23 222 6.582378 4.8269e−11 0.238288 0.103638 58 59 26 16.589 QxxxQ HhhhC 119.4 51.9 424.3 9.99265 1.7280e−23 0.281405 0.122406 145 169 131 14.893 QAxxS HHhhH 58.8 25.6 440.6 6.767101 1.3211e−11 0.133454 0.058061 69 60 44 7.414 ExxxxY HhhccC 53.4 23.3 395.2 6.443766 1.1723e−10 0.135121 0.058842 68 76 65 18.62 SxSE ChHH 61.7 26.9 315.1 7.001886 2.5790e−12 0.195811 0.085508 64 72 60 13.789 IxxxN HhhhH 403.8 176.6 2697.7 17.68693 5.2702e−70 0.149683 0.065459 446 502 358 79.725 ADG HCC 52.2 22.8 214.2 6.502539 8.1955e−11 0.243697 0.106591 57 62 34 3.587 FxxxC HhhhH 53 23.2 1300.9 6.246268 4.0873e−10 0.040741 0.017826 59 63 47 15.836 FxxxH HhhhC 50.3 22 431 6.187233 6.0903e−10 0.116705 0.051087 61 67 57 11.829 NxxxxS CcchhH 59.7 26.1 436.5 6.769024 1.2951e−11 0.13677 0.059891 63 71 57 21.808 ISxE CChH 56.6 24.8 386.1 6.605482 3.9718e−11 0.146594 0.064198 65 62 55 4.591 TxxxxE CcchhH 153.7 67.3 1094.5 10.86893 1.6117e−27 0.140429 0.061501 174 194 152 29.804 YxxxL HhhhH 540.6 236.8 6880.9 20.08853 9.0430e−90 0.078565 0.034417 570 655 461 161.173 IxxxT CchhH 78.9 34.6 681.3 7.739718 9.8608e−15 0.115808 0.050735 83 86 62 31.31 QxxxD HhhhH 1521.3 666.8 5548.2 35.2777  1.3372e−272 0.274197 0.120187 1434 1841 1141 196.522 KxDK EeEE 103.4 45.3 400.6 9.155613 5.5926e−20 0.258113 0.113187 114 39 4 10.641 SxKV CeEE 74.8 32.8 361.7 7.687742 1.5248e−14 0.206801 0.090709 80 29 3 8.036 QxxAA HhhHH 119.9 52.6 1024 9.528485 1.5740e−21 0.11709 0.051362 138 153 120 19.495 ExxRL HhhHH 194.4 85.3 1592.4 12.14393 6.0904e−34 0.12208 0.053562 211 224 175 28.72 PxxH ChhH 61.7 27.1 261.6 7.012657 2.4020e−12 0.235856 0.103682 62 80 54 9.925 SxxQA HhhHH 53.7 23.6 382.6 6.394275 1.6075e−10 0.140355 0.0617 55 66 46 13.703 LSxxE HHhhH 56.5 24.8 444.2 6.537592 6.2004e−11 0.127195 0.055922 65 68 59 13 TKxxxK EEeeeE 67 29.5 480.9 7.130159 9.9543e−13 0.139322 0.061317 77 18 2 5.808 QxxxxE CcchhH 111.8 49.3 708.3 9.23359 2.6009e−20 0.157843 0.069571 125 135 91 12.001 YxxxR HhhhC 88.3 39 494.7 8.228505 1.8953e−16 0.178492 0.07881 114 123 99 13.731 SxY ChH 163.2 72.1 829.5 11.22067 3.2336e−29 0.196745 0.086964 159 192 116 32.32 TxAE ChHH 127.2 56.2 609.9 9.932803 3.0165e−23 0.208559 0.092199 139 163 100 18.244 AxxxxI HhhccC 52.8 23.3 1142.1 6.160343 6.9870e−10 0.046231 0.020438 78 79 68 18.502 NxxE EhhH 79.8 35.3 312.4 7.94677 1.9603e−15 0.255442 0.113064 87 91 49 14.814 YPS CCC 75.2 33.3 377 7.598203 3.0137e−14 0.199469 0.088388 78 73 52 18.633 YxxxS HhhhC 68.2 30.2 392.2 7.190393 6.4338e−13 0.173891 0.077062 77 87 68 19.096 NxxxQ HhhhH 622.8 276.1 2608.8 22.07021  6.1727e−108 0.23873 0.105815 600 741 460 139.721 ExxxxR CchhhH 96.4 42.8 631.6 8.492481 1.9932e−17 0.152628 0.067721 108 133 90 12.676 RxxxAE HhhhHH 57.2 25.4 630.5 6.432535 1.2154e−10 0.090722 0.040326 59 65 55 14.205 AExxS HHhhH 69 30.7 525.3 7.131241 9.7365e−13 0.131354 0.058394 79 89 71 7.484 HxxL HhhC 56.6 25.2 374.6 6.485005 8.7495e−11 0.151095 0.067203 63 70 47 11.112 GxxxxE CchhhH 70.2 31.2 512.7 7.194858 6.1244e−13 0.136922 0.06092 79 98 68 10.557 HxxxR HhhhH 321.8 143.5 1583.7 15.60741 6.4283e−55 0.203195 0.090614 325 388 273 61.605 ExxRR HhhHH 299.8 133.8 1539.6 15.02431 5.0311e−51 0.194726 0.086878 327 382 294 72.254 ARxxQ HHhhH 63.9 28.5 473.6 6.834976 8.0075e−12 0.134924 0.060212 67 74 52 15.525 QxxxG HhhhC 264.2 118.1 1288.7 14.10751 3.3809e−45 0.205013 0.091634 274 318 203 46.677 LxxxH HhhhH 363.9 162.7 3238 16.18427 6.2530e−59 0.112384 0.05025 367 465 281 141.562 SPxxL ECceE 58.9 26.4 269 6.675323 2.4694e−11 0.218959 0.097969 66 43 3 5 NxED ChHH 68.8 30.8 317.4 7.204843 5.8007e−13 0.216761 0.097047 68 76 56 7.524 YxxxR CchhH 55.5 24.9 290.4 6.425431 1.3030e−10 0.191116 0.085617 59 64 49 11.822 QxxxR HhhhH 1090.8 488.7 4100.8 29.02094  3.6056e−185 0.265997 0.11917 1033 1295 830 179.836 IxxE EccE 51.4 23 281.9 6.168465 6.8170e−10 0.182334 0.081702 58 59 43 6.574 AxxxxV HhhccC 75.2 33.7 1390.6 7.236538 4.3596e−13 0.054077 0.024235 109 116 95 16.603 SxxxxQ CcchhH 97.8 43.8 663.1 8.432856 3.2796e−17 0.147489 0.066115 119 126 102 10.513 TxxDK EeeEE 91.2 40.9 412.9 8.290419 1.1242e−16 0.220877 0.099016 103 25 2 11.391 KxxDG EccCC 71.2 31.9 339.7 7.29748 2.9121e−13 0.209597 0.094033 89 96 74 13.514 WxxxT HhhhH 96.5 43.3 984.1 8.269284 1.2892e−16 0.098059 0.043997 110 112 80 31.021 RxxxxR EccccC 59.9 26.9 352.7 6.623809 3.4346e−11 0.169833 0.076235 63 68 45 10.813 ExxGL HhhCC 56.2 25.2 392.3 6.371708 1.8190e−10 0.143258 0.064332 65 70 61 6.371 DxxxxQ CcchhH 85.9 38.7 553.6 7.871355 3.4039e−15 0.155166 0.069878 98 107 90 14.997 FxxxR HhhhH 380.5 171.4 2686.2 16.50728 3.1248e−61 0.14165 0.063807 403 441 312 92.055 TKxD EEeE 103.5 46.7 416.7 8.823218 1.1095e−18 0.24838 0.112045 117 40 4 13.641 LxxxE CchhH 488.7 220.5 3253.3 18.7016 4.6170e−78 0.150217 0.067791 535 608 440 81.17 RxxxR HhhhH 1627.7 735 5837.9 35.21812  1.0581e−271 0.278816 0.125905 1405 1795 1078 376.551 FxxxS HhhhH 203 91.7 2171.4 11.87273 1.5498e−32 0.093488 0.04224 223 240 192 43.44 ExxT EccE 55 24.9 180.7 6.491457 8.6501e−11 0.304372 0.137879 54 68 36 9.01 IxxxR CchhH 71.2 32.3 512.5 7.082769 1.3566e−12 0.138927 0.062944 76 87 67 18.638 FxxxY HhhhH 156.2 70.9 2194.5 10.29735 6.7695e−25 0.071178 0.03231 176 182 141 69.566 YxxxxK EecccC 59.1 26.8 527.3 6.393258 1.5451e−10 0.11208 0.050891 65 70 51 15.317 QxxxQ HhhhH 1076.2 488.7 4171 28.28569  5.1236e−176 0.25802 0.117162 997 1232 812 173.938 RxxxxL HhhccC 95.2 43.3 774.6 8.128103 4.1443e−16 0.122902 0.055843 114 129 103 14.173 NxxxxQ CcchhH 89.8 40.8 601.9 7.943062 1.8903e−15 0.149194 0.0678 99 109 83 27.066 AxxAQ HhhHH 79.5 36.2 761.4 7.381135 1.4828e−13 0.104413 0.04751 84 92 74 11.5 SxM ChH 80.7 36.8 401.4 7.605818 2.7538e−14 0.201046 0.09156 79 91 63 19.888 VGG ECC 71.2 32.4 623.7 6.989302 2.6159e−12 0.114157 0.052013 85 99 59 13.694 MxxxN HhhhH 155.3 70.8 1069.5 10.40015 2.3558e−25 0.145208 0.066161 170 189 149 41.172 HxxxxD CcchhH 56.9 25.9 444.9 6.267277 3.4999e−10 0.127894 0.058283 64 69 42 13.693 PxG HhC 90.2 41.1 292 8.254118 1.5418e−16 0.308904 0.140865 87 103 72 16.132 RxxxxL HhhhcC 87.5 39.9 702.4 7.752774 8.5135e−15 0.124573 0.056842 107 115 88 22.073 SLxxE HHhhH 67.4 30.8 603.2 6.778556 1.1465e−11 0.111737 0.051012 71 76 58 13.349 TxxQ EhhH 58.8 26.9 230.1 6.560384 5.3148e−11 0.255541 0.116691 61 71 49 12.494 QxxDA HhhHH 63.6 29.1 395.9 6.658707 2.6485e−11 0.160647 0.073381 67 69 46 14.471 FxxxN HhhhC 91 41.6 668.6 7.907795 2.4834e−15 0.136105 0.062228 104 116 92 17.061 QxxxxP HhhccC 70.8 32.4 471.6 6.990638 2.6072e−12 0.150127 0.068702 88 89 70 11.521 SPxS ECcE 55.3 25.3 221.9 6.331376 2.3956e−10 0.249211 0.114087 62 38 7 4 QxxxH HhhhH 270.5 123.8 1263.5 13.8755 8.6154e−44 0.214088 0.098019 276 333 215 63.926 NxxQ ChhH 332 152.1 1273.8 15.54405 1.7117e−54 0.260637 0.11941 328 391 253 68.333 ExxxAE HhhhHH 82.6 37.8 768.2 7.460296 8.0982e−14 0.107524 0.049269 90 97 82 15.236 WxR EcC 53.9 24.7 209.1 6.256836 3.8814e−10 0.257771 0.11812 53 64 36 20.081 HxxxE HhhhH 519.1 238.2 2247.4 19.25348 1.2780e−82 0.230978 0.10597 518 620 389 108.313 AxxLQ HhhHH 64.5 29.6 881.6 6.524433 6.3403e−11 0.073162 0.033578 62 57 47 5.807 NTK CEE 60.7 27.9 192.9 6.723444 1.7833e−11 0.314671 0.144478 65 35 7 7.334 YxxxxG EecccC 128.5 59.1 1454.7 9.226183 2.6007e−20 0.088334 0.040595 147 156 100 35.882 DxxxxR CcchhH 80.6 37.1 502.2 7.433222 1.0069e−13 0.160494 0.073783 94 110 77 21.917 VDKK EEEE 78.6 36.1 374.6 7.42806 1.0634e−13 0.209824 0.0965 90 26 1 8.308 SxxxxE CcchhH 192.1 88.4 1305.4 11.42485 2.9571e−30 0.147158 0.06771 218 247 163 34.29 NxF ChH 105.6 48.6 612.6 8.517471 1.5500e−17 0.17238 0.079361 111 102 68 30.672 PxxxxR CchhhH 112.2 51.7 866.2 8.68564 3.5307e−18 0.129531 0.059641 127 145 107 30.249 SxAD ChHH 93.1 42.9 534.3 7.998864 1.1948e−15 0.174247 0.080239 105 105 80 26.811 ExxxR HhhhH 3545.7 1634.5 12751.1 50.62821 0.0000e+00 0.27807 0.128187 3009 4163 2328 605.848 RxxV HhhC 93.3 43 530.2 7.995811 1.2235e−15 0.175971 0.08115 104 114 95 19.625 RxxxQ HhhhC 158.8 73.3 541.1 10.74695 6.0389e−27 0.293476 0.135401 191 217 149 24.372 RxxDG EccCC 67.2 31 359.2 6.792614 1.0513e−11 0.187082 0.086392 84 88 64 12.849 TxxxQ HhhhH 624.6 288.5 2880.6 20.86151 1.1458e−96 0.21683 0.100147 598 678 467 118.683 YxxxxK HhhhcC 68.3 31.5 611.7 6.718956 1.7065e−11 0.111656 0.051574 78 84 69 13.984 SxxxxS CcchhH 63.2 29.2 600.9 6.451142 1.0335e−10 0.105176 0.048591 69 80 60 31.067 AxxAR HhhHH 118.4 54.8 1244.1 8.783439 1.4619e−18 0.095169 0.044062 130 140 111 22.224 AAxxQ HHhhH 100.7 46.6 848.8 8.140927 3.6432e−16 0.118638 0.054957 122 127 99 32.506 AxxxxQ CcchhH 85.1 39.4 713.6 7.484263 6.6905e−14 0.119254 0.055247 104 108 83 18.21 ETG HHC 74.9 34.7 331.4 7.207961 5.4644e−13 0.226011 0.104757 90 97 65 15.125 SxxxxL HhhhhC 67.1 31.1 827.3 6.577482 4.4042e−11 0.081107 0.037604 81 85 67 22.607 YxxxS HhhhH 214.8 99.6 1731.9 11.88306 1.3421e−32 0.124026 0.057535 218 259 183 47.88 AxxQQ HhhHH 73.7 34.2 442.5 7.033591 1.8980e−12 0.166554 0.077271 81 92 68 13.121 AxxxQ HhhhC 159.9 74.2 882.2 10.39559 2.4485e−25 0.181251 0.084109 186 203 140 22.602 ExxxxQ CcchhH 78.9 36.6 518.6 7.24759 3.9788e−13 0.15214 0.070611 92 94 83 10.679 DxxxR HhhhH 1593.6 739.8 6057.4 33.50368  4.1121e−246 0.263083 0.12213 1505 1906 1138 277.568 AAxG HHhC 75.4 35 497.1 7.073599 1.4144e−12 0.15168 0.070477 89 100 78 15.642 FxxE ChhH 60.5 28.1 344.2 6.366639 1.8254e−10 0.17577 0.081749 69 76 60 12.197 DDxxR HHhhH 61.8 28.8 348.8 6.430871 1.1980e−10 0.177179 0.082463 63 72 53 15.074 IxxxQ HhhhH 400.2 186.3 3042.8 16.17444 7.0518e−59 0.131524 0.061226 430 478 342 81.324 TxxxxQ CcchhH 74.5 34.7 567.5 6.969533 2.9520e−12 0.131278 0.061168 84 93 70 13.997 RxxxL HhhhC 172.6 80.5 831.2 10.80681 3.0229e−27 0.207652 0.096811 213 241 190 27.718 GxxxxE CcchhH 400.5 186.8 2725.7 16.19978 4.6835e−59 0.146935 0.068536 454 524 390 76.391 RAxG HHcC 86.6 40.4 412 7.653312 1.8592e−14 0.210194 0.09806 103 119 91 9.868 LxxxxL HhhhcC 62.6 29.2 1199.2 6.256042 3.5831e−10 0.052201 0.024354 85 125 69 27.266 YRD CCC 56.6 26.4 267.9 6.182857 5.9939e−10 0.211273 0.098638 54 66 36 25.66 AxxxY HhhcC 58.6 27.4 444.2 6.164994 6.5438e−10 0.131923 0.061597 70 81 62 14.158 YxGG CcCC 59 27.6 473.8 6.172162 6.2375e−10 0.124525 0.05816 67 68 43 24.891 VxxxN HhhhH 437.6 204.7 2937.8 16.8822 5.6161e−64 0.148955 0.069662 457 507 342 94.476 DxxxR HhhhC 205.1 961 824.3 11.82542 2.7483e−32 0.248817 0.116618 248 266 172 22.767 ExxxW HhhhH 249 116.7 1634.9 12.70221 5.3036e−37 0.152303 0.071408 257 291 212 53.883 HxN ChH 59.7 28 226.7 6.400861 1.4890e−10 0.263344 0.123483 63 72 55 13.091 RxxxQ HhhhH 1065.6 500 4150.3 26.97253  2.9554e−160 0.256753 0.120469 1056 1312 832 186.326 YxxxK HhhhH 681 320.1 3778.3 21.08821 9.4565e−99 0.18024 0.08471 729 824 583 174.419 WxxxK HhhhH 195.9 92.1 1228.6 11.24863 2.1703e−29 0.15945 0.074949 212 249 175 30.575 FxxxL HhhhC 61.4 28.9 908.1 6.148447 7.0691e−10 0.067614 0.031808 76 83 69 21.034 AxxxxL HhhhcC 82.4 38.8 1305.4 7.106322 1.0716e−12 0.063122 0.029722 105 110 100 18.122 TxVD EeEE 116.5 54.9 674.4 8.681155 3.6299e−18 0.172746 0.081358 128 48 12 12.641 HxxxL HhhhH 353.1 166.4 3401.1 14.84586 6.6881e−50 0.103819 0.048913 371 453 320 106.756 LxxxxE CcchhH 116 54.7 1020.9 8.516601 1.4929e−17 0.113625 0.053595 143 148 120 17.066 LAxG HHcC 73.6 34.7 547.8 6.815209 8.6277e−12 0.134356 0.0634 87 87 80 4.742 KxxGL HhcCC 60.1 28.4 463.9 6.148064 7.1894e−10 0.129554 0.061156 73 75 55 7.864 DxxxxR HhhccC 74.8 35.3 488.9 6.897404 4.8780e−12 0.152997 0.072239 88 96 73 16.2 DxR HcC 120.8 57.1 342.9 9.241439 2.3884e−20 0.352289 0.166413 120 144 93 21.057 DxxxR HhhcC 150 70.9 559.5 10.05589 8.2324e−24 0.268097 0.126689 176 195 100 30.026 QGQ CCC 91.8 43.4 358.4 7.828759 4.6739e−15 0.256138 0.121185 89 114 67 23.688 KKxG HHhC 87.7 41.5 381.6 7.588969 3.0299e−14 0.229822 0.108834 96 104 80 14.791 IxxxG HhhhC 159.3 75.4 1532.9 9.900532 3.7296e−23 0.103921 0.049218 182 218 162 32.855 NxxL HhhC 88.6 42 577.8 7.473791 7.1427e−14 0.15334 0.072641 105 115 93 24.064 AxxxxE CcchhH 148 70.1 1242.5 9.57374 9.3271e−22 0.119115 0.056438 182 205 160 23.239 NxxxxK CcchhH 70.7 33.5 463.4 6.67288 2.3023e−11 0.152568 0.072292 80 93 57 15.919 QxxxxK HhhhcC 80.9 38.3 526.8 7.138789 8.6346e−13 0.153569 0.072774 102 111 83 24.241 FxxxM HhhhH 130.3 61.8 2397 8.831735 9.1511e−19 0.05436 0.025775 143 153 110 45.842 IxxxH HhhhH 160.2 76 1637.9 9.889877 4.1336e−23 0.097808 0.046403 171 194 149 38.766 RxxxxR CchhhH 64 30.4 468 6.305957 2.6131e−10 0.136752 0.064928 71 80 62 21.522 SAxxA HHhhH 64.8 30.8 919.3 6.235618 4.0246e−10 0.070488 0.033488 74 86 66 15.231 QxxxL HhhhC 85.3 40.7 488.9 7.293506 2.7633e−13 0.174473 0.083315 102 112 88 11.179 FxxxE HhhhH 345.2 164.9 2494.4 14.52726 7.3232e−48 0.13839 0.066114 362 413 303 77.031 AxxxxK CchhhH 65.6 31.3 553.9 6.29968 2.6877e−10 0.118433 0.056587 86 96 69 13.217 SVT EEE 97.7 46.7 1097.2 7.630634 2.0807e−14 0.089045 0.042549 101 108 61 15.87 SxF HcC 65.2 31.2 400.3 6.340682 2.0860e−10 0.162878 0.077927 85 94 69 20.586 NxxY ChhH 129.4 61.9 713 8.972069 2.6554e−19 0.181487 0.086858 137 153 113 32.324 SIP CCC 122.5 58.7 674 8.717895 2.5843e−18 0.181751 0.087074 138 160 113 26.542 AxxxQ HhhhH 1200.9 575.4 6408.2 27.32937  1.7264e−164 0.187401 0.089798 1143 1371 904 221.614 PxxxN HhhhH 244.4 117.2 1114.8 12.42461 1.7671e−35 0.219232 0.105106 247 278 190 47.738 PAxxA HHhhH 81.8 39.3 821.2 6.958559 3.0611e−12 0.09961 0.047803 97 107 91 17.091 NxxM ChhH 80.1 38.5 489.7 6.994627 2.4124e−12 0.16357 0.078538 80 103 55 23.769 ExxxR HhhhC 358.1 171.9 1395.4 15.16136 5.9193e−52 0.256629 0.123222 418 499 360 54.629 PxxxR HhhhH 719.8 345.7 3048.4 21.37119  2.2826e−101 0.236124 0.113393 701 862 579 114.931 KEG HHC 69.4 33.3 254.1 6.699047 1.9722e−11 0.273121 0.131224 76 88 50 6.688 SxM CcE 75.8 36.4 475.7 6.789208 1.0209e−11 0.159344 0.076571 83 85 47 17.817 ARxxA HHhhH 122.1 58.7 1454.9 8.445356 2.6748e−17 0.083923 0.040353 132 144 120 20.965 LxxxxL HhhccC 97.7 47 2223.4 7.478582 6.5648e−14 0.043942 0.021131 125 146 109 37.694 ExxxxS HhhccC 134.5 64.7 919.1 8.999618 2.0332e−19 0.146339 0.070398 156 177 133 21.65 FxxxH HhhhH 105.8 50.9 1207.8 7.860939 3.3681e−15 0.087597 0.042149 126 136 103 37.372 GxSxE CcChH 87.9 42.3 619 7.264315 3.3686e−13 0.142003 0.068333 101 107 86 23.805 DxxRS HhhHH 61.7 29.7 350.8 6.13944 7.5388e−10 0.175884 0.084643 77 80 61 7.371 GSV CCE 68.4 32.9 455.6 6.418609 1.2407e−10 0.150132 0.072268 78 84 58 14.803 ExxxxR HhhccC 116.1 55.9 742.2 8.375368 4.9567e−17 0.156427 0.075303 145 165 130 26.948 FxxxG HhhhC 124.9 60.2 1209.9 8.555379 1.0397e−17 0.103232 0.049752 146 164 116 26.139 QxxxL HhhhH 851 410.1 7080.9 22.42827  1.8468e−111 0.120182 0.057922 853 962 660 154.311 QxxxY HhhhH 271.3 130.8 1885.2 12.73119 3.5409e−37 0.14391 0.069396 285 331 221 45.473 LxF CcE 75 36.2 816.4 6.588127 3.9326e−11 0.091867 0.044382 79 80 59 18.526 YxxxE CchhH 112.3 54.3 687 8.211157 1.9695e−16 0.163464 0.078974 134 152 114 35.048 ExxxxK CchhhH 94.6 45.7 621.2 7.513633 5.1579e−14 0.152286 0.073579 114 124 91 25.02 QxxxF HhhhH 258.4 125 2416.8 12.25568 1.3787e−34 0.106918 0.051712 267 292 198 57.252 MxxxQ CchhH 65.8 31.8 417.5 6.263424 3.3882e−10 0.157605 0.07625 76 87 71 5.183 HxxxD HhhhH 206.8 100.1 1013.9 11.22807 2.6894e−29 0.203965 0.098763 207 252 176 38.725 KxGxT CcCcC 72 34.9 523.7 6.508995 6.7535e−11 0.137483 0.066578 79 71 44 14.708 PxxxM HhhhH 89.5 43.3 757.8 7.2189 4.6432e−13 0.118105 0.057205 102 106 84 25.723 TxY ChH 85.9 41.6 440.4 7.210357 5.0580e−13 0.19505 0.09453 83 95 60 11.836 RxxxN HhhhH 653.6 316.9 2892.5 20.04073 2.2101e−89 0.225964 0.109571 638 758 493 166.223 TxTG CcCC 114.1 55.4 731.8 8.204551 2.0652e−16 0.155917 0.075694 118 130 77 56.478 NxxH HhhH 180.4 87.6 891.3 10.44351 1.4170e−25 0.202401 0.098269 180 217 148 36.561 YxxxE HhhhH 396.8 192.7 2422.9 15.32313 4.7702e−53 0.163771 0.079539 427 499 343 75.821 VxxxQ CchhH 116.7 56.7 787.6 8.275504 1.1380e−16 0.148172 0.071966 132 144 112 38.882 RExxL HHhhH 112.2 54.5 836.4 8.083483 5.5774e−16 0.134146 0.065161 131 138 113 26.81 NxxxY HhhhH 187.1 90.9 1394.3 10.43545 1.5096e−25 0.134189 0.065196 196 234 161 56.034 EAxxxE HHhhhH 84.2 40.9 815.1 6.93732 3.5127e−12 0.1033 0.050228 89 93 82 20.708 AxF CcE 119.3 58 980.5 8.293706 9.6758e−17 0.121673 0.059176 126 137 89 19.508 PExxR HHhhH 110.7 53.8 655.7 8.086699 5.4810e−16 0.168827 0.082123 126 141 107 14.452 MxxxY HhhhH 108.2 52.7 1431.8 7.795767 5.5677e−15 0.075569 0.036787 109 122 88 40.104 ERxG HHhC 65.2 31.7 305.7 6.27148 3.2513e−10 0.213281 0.103854 76 76 70 10.267 TxxxxN ChhhhH 72.2 35.2 571.7 6.444471 1.0257e−10 0.12629 0.061525 94 101 81 15.818 HxxN HhhH 260.9 127.1 1176.7 12.56098 3.1284e−36 0.221722 0.108046 232 287 167 78.115 SxxxN ChhhH 71.4 34.8 551.2 6.406584 1.3160e−10 0.129536 0.063158 82 88 59 16.96 RxxxE HhhhH 2928.1 1427.8 11214.8 42.50305 0.0000e+00 0.261092 0.127313 2601 3500 2041 525.598 NxxxF HhhhH 155.5 75.8 1607.2 9.369422 6.3552e−21 0.096752 0.047193 161 180 140 39.768 NxxxS HhhhH 514.3 251.1 2512.2 17.50681 1.1392e−68 0.204721 0.099956 526 601 395 70.614 ExxRQ HhhHH 149.6 73.1 886.5 9.344841 8.1784e−21 0.168754 0.082435 158 177 141 21.975 NxF HhC 72.6 35.5 446 6.491726 7.5556e−11 0.16278 0.079585 82 87 71 13.599 SxxxD HhhhC 98.8 48.3 457.9 7.675582 1.4860e−14 0.215768 0.105553 118 132 90 12.446 VNG ECC 97.3 47.6 641 7.485467 6.3078e−14 0.151794 0.07427 111 127 83 24.925 HxxxT HhhhH 192.6 94.3 1244.4 10.53318 5.3588e−26 0.154773 0.075761 192 227 168 35.961 FxxxD CchhH 109.6 53.7 851.1 7.887565 2.7037e−15 0.128775 0.063058 116 133 90 24.115 NxxxN HhhhH 411.8 201.8 1933.5 15.62583 4.3487e−55 0.212982 0.104345 422 490 354 80.053 ExxLS HhhHH 102.2 50.1 839.3 7.584261 2.9242e−14 0.121768 0.059728 112 129 86 14.243 YxA EeC 123.8 60.8 897.4 8.374344 4.8699e−17 0.137954 0.067715 132 137 87 28.11 GxxxxK CcchhH 153.6 75.4 1023 9.34895 7.7771e−21 0.150147 0.07375 174 189 148 33.669 LSE CCH 67.5 33.2 383.7 6.23691 3.9711e−10 0.175919 0.086443 73 80 62 10.044 KVxK EEeE 129 63.4 665.5 8.662445 4.1119e−18 0.193839 0.09526 148 68 22 13.372 AxxER HhhHH 160.2 78.8 960 9.579453 8.6052e−22 0.166875 0.082033 183 187 143 28.163 LxxxQ HhhhH 838.5 412.3 6031.4 21.74665  6.4761e−105 0.139022 0.068358 850 997 687 139.608 NxxxG HhhhC 114.1 56.1 662.4 8.090558 5.2533e−16 0.172252 0.084717 131 151 116 19.267 DExxR HHhhH 151.9 74.7 886.6 9.330064 9.3406e−21 0.171329 0.08428 178 190 132 23.764 HxS ChH 120.6 59.3 487.3 8.485009 1.9520e−17 0.247486 0.121783 122 142 94 47.563 RxxxxD HhhccC 174.6 85.9 1073.5 9.970399 1.8063e−23 0.162646 0.080061 201 218 156 37.795 NxA ChH 528.3 260.2 2030.4 17.79765 6.6617e−71 0.260195 0.128165 527 651 418 107.697 RxxxM HhhhH 316.3 155.8 2095.9 13.3639 8.5903e−41 0.150914 0.074339 338 384 276 66.921 EAxG HHcC 82.7 40.7 436.1 6.903283 4.5200e−12 0.189635 0.093429 102 118 89 12.2 QxF EeE 222 109.4 1489.4 11.18519 4.2124e−29 0.149053 0.073447 230 258 153 59.238 NxY ChH 107.4 52.9 534.1 7.884635 2.8091e−15 0.201086 0.099131 114 124 96 17.744 WxxxS HhhhH 82.7 40.8 958.5 6.709178 1.6880e−11 0.086281 0.042544 93 111 71 32.016 NxxD HhhC 65.7 32.5 306.6 6.16967 6.1279e−10 0.214286 0.105875 73 74 52 10.337 AxxxQ CchhH 130.5 64.5 770.7 8.587977 7.7782e−18 0.169327 0.08367 142 151 108 16.149 PxxQ ChhH 241 119.4 891.4 11.96006 5.1935e−33 0.270361 0.13393 247 296 186 41.075 SxA ChH 850.1 421.1 3347.3 22.35703  9.2441e−111 0.253966 0.125812 844 989 615 158.146 AAxxR HHhhH 129.8 64.3 1242.9 8.387023 4.2884e−17 0.104433 0.051739 151 173 118 22.819 TxA ChH 715.6 354.6 2588.8 20.63903 1.1060e−94 0.276422 0.13696 686 858 491 130.016 LPxE CChH 68.7 34 555.4 6.130691 7.5993e−10 0.123695 0.061295 83 92 77 8.37 QxxxE HhhhC 174.5 86.5 667.8 10.13754 3.3887e−24 0.261306 0.129565 221 243 193 32.093 SxxxxR ChhhhH 261 129.5 1853.7 11.98243 3.8015e−33 0.140799 0.069857 294 311 234 48.458 QxxxM HhhhH 197.5 98 1607.1 10.37229 2.8562e−25 0.122892 0.060979 210 223 171 43.25 FxA CcH 93.2 46.2 622.7 7.175335 6.2867e−13 0.149671 0.074273 106 100 69 24.295 RRxxA HHhhH 86.1 42.7 559.3 6.903535 4.4287e−12 0.153942 0.0764 93 106 88 18.855 AAG HCC 163.7 81.2 702.7 9.726602 2.0695e−22 0.232959 0.115625 186 217 165 35.286 RxxxH HhhhH 331.8 164.7 1574.4 13.75929 3.9545e−43 0.210747 0.104616 343 393 284 91.04 KAxG HHcC 86.7 43.1 434.8 7.007685 2.1431e−12 0.199402 0.099021 105 123 93 12.619 SxxG EccE 85.4 42.4 515.1 6.890972 4.8521e−12 0.165793 0.082335 93 101 56 16.833 NxxxL HhhhH 450.7 223.9 4154.2 15.57809 8.7727e−55 0.108493 0.053909 464 574 354 121.326 SxxxQ HhhhH 680.2 338 3360 19.62634 8.0947e−86 0.20244 0.100596 708 826 541 113.599 VxxxE CchhH 245.6 122.1 1615.1 11.61904 2.8573e−31 0.152065 0.075624 271 323 228 40.287 YxxxD HhhhH 157.6 78.4 997.2 9.32088 1.0028e−20 0.158043 0.078606 154 171 131 51.967 TFP CCC 67.2 33.4 373.1 6.119638 8.2482e−10 0.180113 0.089618 71 71 51 18.232 DxxxW HhhhH 115.7 57.6 860.6 7.929366 1.9031e−15 0.134441 0.066906 129 142 113 26.428 PxN ChH 1922 95.7 703.2 10.61399 2.3079e−26 0.273322 0.136083 201 242 139 32.479 TxxxG HhhhC 132.9 66.2 909 8.507609 1.5359e−17 0.146205 0.072863 160 179 129 28.082 MxxxR HhhhH 285.5 142.3 1901.9 12.48189 8.0946e−36 0.150113 0.074814 303 360 254 58.722 WxN EeC 79.3 39.5 468.5 6.61109 3.3332e−11 0.169264 0.08437 90 103 58 28.048 VxxxT CchhH 99.3 49.5 842.9 7.295684 2.5533e−13 0.117808 0.058726 111 125 95 29.562 ExxxxE CcchhH 191.6 95.5 1299.3 10.21315 1.4953e−24 0.147464 0.073517 221 231 184 34.126 AxxRA HhhHH 165.8 82.7 1804.6 9.359131 6.8374e−21 0.091876 0.045813 181 196 152 34.61 DxxxxP HhhccC 81.2 40.5 566.5 6.632996 2.8486e−11 0.143336 0.071521 99 106 76 12 YxxxV HhhhH 261.5 130.5 3516 11.68707 1.2533e−31 0.074374 0.037115 270 307 224 73.847 ExxxxR HhcccC 91.4 45.6 570.5 7.067226 1.3740e−12 0.16021 0.079958 107 110 92 25.338 AxxQR HhhHH 73 36.5 485.4 6.292274 2.7145e−10 0.150391 0.075114 83 97 75 12.836 IxxxD HhhhH 254.3 127.1 1867.9 11.69002 1.2299e−31 0.136142 0.068034 254 301 218 48.416 NxxxxD CcchhH 109.2 54.6 880.8 7.633463 1.9605e−14 0.123978 0.061967 124 132 101 24.306 WxxxL HhhhH 145.8 72.9 2398.9 8.665128 3.7936e−18 0.060778 0.030403 161 181 139 25.481 WxxE HhhH 321.8 161.2 1855.3 13.24235 4.3211e−40 0.173449 0.086864 333 381 277 57.781 FPG CCC 138.7 69.5 857.5 8.66519 3.8961e−18 0.161749 0.08101 145 154 109 30.1 YH EC 69.6 34.9 354.8 6.193445 5.1633e−10 0.196167 0.098282 67 80 49 14.582 DxxxxE CcchhH 154.5 77.4 1117.3 9.079327 9.3679e−20 0.13828 0.069298 177 204 160 36.074 QxxR ChhH 74.6 37.4 275.8 6.539894 5.5204e−11 0.270486 0.135645 82 89 58 27.364 LGL HCC 74.7 37.5 580.4 6.283761 2.8353e−10 0.128704 0.064592 89 91 82 13.4 PGY CCC 82.9 41.6 425.5 6.738554 1.3978e−11 0.19483 0.097795 88 98 77 17.918 HxxxI HhhhH 127.4 64 1572.2 8.093262 4.8957e−16 0.081033 0.040701 142 153 122 38.735 AExxQ HHhhH 100.1 50.3 642.7 7.316766 2.1891e−13 0.155749 0.078242 106 116 92 17.982 ExxAS HhhHH 78.3 39.4 631.6 6.411106 1.2354e−10 0.123971 0.062309 84 105 70 21.553 DxxRQ HhhHH 84.9 42.7 458.7 6.78259 1.0263e−11 0.185088 0.093078 95 101 77 17.416 ExxxF HhhcC 77.4 38.9 528.7 6.406402 1.2815e−10 0.146397 0.07363 94 106 86 11.703 AExG HHhC 70.3 35.4 410.4 6.143817 6.9830e−10 0.171296 0.086186 85 102 80 15.625 ASG HCC 79.4 40 365.1 6.610071 3.3716e−11 0.217475 0.109465 82 89 67 27.147 DAA CHH 69.4 34.9 328.4 6.165825 6.1475e−10 0.211328 0.10641 74 93 54 9.497 KxxxxN HhhccC 132.1 66.5 806.8 8.389233 4.2077e−17 0.163733 0.082483 155 171 124 23.736 QxxxS HhhhH 623.3 314 3007.9 18.44224 5.2220e−76 0.207221 0.104399 641 765 493 120.461 IxxxE HhhhH 652.2 328.6 4866.2 18.48686 2.2361e−76 0.134027 0.067526 672 799 570 137.019 QxxxT HhhhH 555.2 279.9 2775.6 17.35473 1.5715e−67 0.200029 0.100838 576 659 427 105.928 FxxxL HhhhH 426.4 215.1 9230.4 14.57674 3.2704e−48 0.046195 0.023305 463 470 340 97.989 VxxxxL CchhhH 80.9 40.8 2037.1 6.338101 1.9368e−10 0.039713 0.020036 101 106 82 21.898 QxxR HhhC 128.7 65 477.4 8.509002 1.5563e−17 0.269585 0.136064 137 156 112 23.243 TxxxY HhhhH 213.6 107.8 2022 10.47044 9.9480e−26 0.105638 0.053322 239 260 177 84.626 NF HC 110.1 55.6 503.5 7.750356 8.0006e−15 0.218669 0.110418 112 141 92 15.526 DH HC 131.5 66.4 320.4 8.971856 2.7193e−19 0.410424 0.207256 129 157 111 22.973 QxxER HhhHH 70.7 35.7 399.7 6.137637 7.2446e−10 0.176883 0.089324 71 79 64 15.047 DAG HCC 85.4 43.1 354.4 6.866307 5.8013e−12 0.240971 0.121717 98 115 78 10.867 QQxxA HHhhH 78 39.4 558.3 6.368381 1.6309e−10 0.13971 0.070648 86 99 69 9.346 LxxxT CchhH 95.4 48.3 871.5 6.983018 2.4411e−12 0.109466 0.055369 108 117 96 28.085 QAxxD HHhhH 99.7 50.5 702.9 7.189078 5.5537e−13 0.141841 0.071827 112 122 98 13.289 KxxxxR CchhhH 83.4 42.2 572.5 6.58186 3.9651e−11 0.145677 0.073771 99 107 77 16.931 SxEQ ChHH 106.6 54 926.8 7.379054 1.3464e−13 0.115019 0.058249 114 129 86 22.79 QxW EeE 94.4 47.9 664.8 6.985402 2.4170e−12 0.141998 0.071977 94 109 66 30.429 RxxxE HhhhC 308.8 156.5 1155 13.08793 3.3953e−39 0.267359 0.135538 389 450 331 52.801 NxxL ChhH 281.7 142.8 1993.4 12.05842 1.4819e−33 0.141316 0.071657 301 341 257 59.804 IxxxR HhhhH 603.5 306 4707.3 17.58507 2.6989e−69 0.128205 0.065013 644 748 514 134.938 SxxxG HhhhC 189.6 96.2 1456 9.861034 5.1865e−23 0.13022 0.066039 212 252 180 40.425 ExxxQ HhhhH 1903.9 965.9 7773.1 32.25062  3.0026e−228 0.244934 0.124264 1811 2315 1395 311.531 QxP EeC 114.4 58 719.8 7.713629 1.0432e−14 0.158933 0.080647 133 120 52 15.896 SxxM ChhH 89.2 45.3 602.1 6.789937 9.5554e−12 0.148148 0.075183 94 105 82 20 SxxxL HhhcC 74.1 37.6 549.3 6.158948 6.2187e−10 0.134899 0.068513 89 100 81 21.314 NPT CCC 103 52.3 577.1 7.347429 1.7329e−13 0.178479 0.090661 107 117 61 12.992 GxxQ ChhH 163.5 83.1 829.6 9.303796 1.1657e−20 0.197083 0.100124 173 204 138 30.525 NxxN ChhH 243.7 123.8 1030.3 11.48567 1.3538e−30 0.236533 0.120178 252 299 180 56.967 RxxxxP HhhccC 119.3 60.6 837.7 7.825423 4.2887e−15 0.142414 0.072363 156 170 129 28.616 SxQ ChH 428.7 217.8 1547 15.41239 1.1886e−53 0.277117 0.140817 430 513 345 65.108 ExLG HhHC 117.4 59.7 783.8 7.773841 6.4656e−15 0.149783 0.076139 147 151 126 22.062 YxxxT HhhhH 198.7 101.1 1762.5 10.00453 1.2198e−23 0.112738 0.057336 216 230 159 40.009 SEA CHH 80.7 41.1 343 6.595633 3.6965e−11 0.235277 0.119681 91 100 75 13.436 SxxxR HhhhH 800.7 407.6 4098.8 20.52142 1.1851e−93 0.19535 0.099432 814 960 651 163.053 LxxxN HhhhC 162.3 82.7 1288.9 9.05616 1.1357e−19 0.125921 0.064126 188 203 159 31.187 LxxxR HhhhH 1256.2 640.3 9084.4 25.24464  1.0887e−140 0.138281 0.070486 1290 1519 1082 248.703 ExxR HhhH 4348.2 2217.2 15346 48.92995 0.0000e+00 0.283344 0.144479 3640 5115 2655 709.592 RxxxF HhhhH 272.8 139.1 2338.6 11.68438 1.2799e−31 0.116651 0.059496 289 325 244 64.798 ALG HHC 97.2 49.6 629.4 7.045039 1.5728e−12 0.154433 0.078782 124 136 105 19.697 SxDE ChHH 97.5 49.7 519.2 7.121477 9.1460e−13 0.187789 0.095803 99 113 88 16.819 TxxxN HhhhC 105 53.6 580 7.371169 1.4445e−13 0.181034 0.0924 127 141 104 12.344 ExxxY HhhhH 629.3 321.2 3734.6 17.97894 2.4098e−72 0.168505 0.086016 649 764 489 132.972 RxxxxN HhcccC 81 41.4 530.9 6.420158 1.1549e−10 0.152571 0.077895 93 104 61 6.844 DxxxxQ ChhhhH 152.3 77.8 1117.8 8.75111 1.7751e−18 0.13625 0.06963 173 184 159 30.431 LxxxY HhhhH 436.4 223 6456.4 14.54017 5.5425e−48 0.067592 0.034545 424 494 322 142.511 QxxC HhhH 102.3 52.3 908 7.121624 8.9199e−13 0.112665 0.057601 111 114 75 26.926 PxS EhH 130.1 66.5 449.4 8.442109 2.7448e−17 0.289497 0.148061 139 154 54 29.149 SxxE EhhH 86.7 44.4 455.6 6.691661 1.8876e−11 0.190299 0.097361 90 102 80 12.275 WxxQ HhhH 174.6 89.4 1173.3 9.380752 5.5115e−21 0.148811 0.076165 198 232 142 42.633 TxxxR HhhhH 665.8 341.1 3439.7 18.52247 1.1550e−76 0.193563 0.099169 684 772 543 132.037 SxxQ ChhH 506 259.3 2528 16.17084 6.8893e−59 0.200158 0.102577 508 612 382 71.886 QExxA HHhhH 89.4 45.8 602.2 6.698367 1.7776e−11 0.148456 0.076085 101 107 86 12.412 NxxxI HhhhH 188 96.5 2023 9.548308 1.0890e−21 0.092931 0.04769 181 216 156 46.585 AxxDA HhhHH 99.9 51.3 1121.1 6.945769 3.1146e−12 0.089109 0.045761 113 123 106 17.081 RxxxxE HhcccC 98.1 50.4 624.8 7.004826 2.0838e−12 0.15701 0.080687 118 132 108 16.112 VxxxQ HhhhH 449.5 231 3342.8 14.89745 2.8501e−50 0.134468 0.069112 470 537 380 90.195 HxxxM HhhhH 95.5 49.1 883.3 6.814365 7.8684e−12 0.108117 0.055585 103 107 81 23.829 KYG HHC 97.9 50.3 426.2 7.139373 8.0699e−13 0.229704 0.118099 112 125 83 16.329 EExG HHhC 98.4 50.6 520 7.065914 1.3554e−12 0.189231 0.097369 121 145 109 15.932 NxQ EcC 117.5 60.5 485.7 7.832707 4.1145e−15 0.241919 0.124557 122 138 80 24.775 RxxxD HhhhH 1124.8 579.6 4662.5 24.19752  2.0224e−129 0.241244 0.12432 1106 1350 903 210.134 DxY ChH 151.5 78.1 697.2 8.818579 9.8907e−19 0.217298 0.11198 158 182 134 35.046 ExxxF HhccC 104.5 53.9 703.6 7.170991 6.2323e−13 0.148522 0.076616 127 124 95 22.902 PxxxE CchhH 317.3 163.7 1905.6 12.55449 3.1445e−36 0.166509 0.085914 345 384 267 61.567 VxxxxE CcchhH 89.2 46 874.3 6.538549 5.1382e−11 0.102024 0.052642 119 127 113 27.383 AQxxA HHhhH 97 50.1 1116.6 6.788691 9.3146e−12 0.086871 0.044831 115 134 101 19.916 EAxxA HHhhH 202.1 104.3 2020.6 9.828707 6.9670e−23 0.10002 0.051634 234 262 217 31.039 MxxxD HhhhH 153.4 79.2 1113.4 8.646793 4.4054e−18 0.137776 0.071156 179 190 141 37.128 NxxxT HhhhH 370.4 191.4 2062 13.58795 3.9615e−42 0.179631 0.092806 377 434 297 56.147 AGP CCC 129.7 67 642.9 8.089518 5.0769e−16 0.201742 0.104248 135 152 92 46.054 RxxxE CchhH 240.9 124.5 1092.3 11.07871 1.3526e−28 0.220544 0.114007 256 294 223 48.713 QAG HCC 72.9 37.7 291.4 6.147215 6.8091e−10 0.250172 0.129331 81 87 67 10.542 YxxxG HhhhC 130.4 67.4 1073.6 7.92034 1.9602e−15 0.121461 0.062812 146 170 128 22.109 RxxxI HhhcC 83.8 43.4 545.9 6.399601 1.3039e−10 0.153508 0.079439 100 95 76 12.163 HH HC 98.4 50.9 263.6 7.406467 1.1640e−13 0.373293 0.193191 111 122 97 18.524 RRxxE HHhhH 190.5 98.6 1055.7 9.717855 2.1236e−22 0.180449 0.093412 196 232 157 51.463 IxxxR HhhhC 78 40.4 663.7 6.108153 8.3534e−10 0.117523 0.060846 92 93 74 14.325 AxxxR HhhhH 1716.6 888.8 9975.9 29.09357  3.6109e−186 0.172075 0.089093 1654 2079 1299 330.422 RxxAL HhhHH 97.3 50.4 1236.5 6.745354 1.2494e−11 0.07869 0.04076 103 117 94 25.818 VxxxE HhhhH 776.9 402.6 5432.9 19.38376 8.7489e−84 0.142999 0.074111 810 954 665 148.632 NxxxH HhhhH 153.4 79.5 868.2 8.690635 3.0194e−18 0.176687 0.091605 158 182 134 32.63 GxW CeE 139.7 72.4 765.8 8.306914 8.2462e−17 0.182424 0.09458 141 158 102 52.85 IPS CCC 86.4 44.8 533.7 6.489723 7.1959e−11 0.161889 0.083976 103 120 80 17.239 KxxxL HhhhH 1346.1 698.5 9345.2 25.47497  3.0835e−143 0.144042 0.074742 1360 1568 1105 261.265 DxY EeE 220.1 114.3 1491.6 10.29625 6.0672e−25 0.14756 0.07664 237 253 156 49.973 SxxxN HhhhH 487.3 253.1 2480.3 15.53476 1.6921e−54 0.196468 0.102045 506 585 397 85.22 RxxxI HhccC 83 43.1 667.3 6.28049 2.7918e−10 0.124382 0.064612 113 125 104 20.075 TxxxF HhhhH 143.7 74.8 2434.2 8.087854 4.9079e−16 0.059034 0.030738 151 194 129 47.689 QxxID HhhHH 80.6 42 759.4 6.135319 6.9812e−10 0.106136 0.055264 93 99 79 10.301 ExxR HhhC 380.1 197.9 1322.8 14.04151 7.4744e−45 0.287345 0.14963 420 499 318 62.185 PGP CCC 141.6 73.8 708.1 8.3469 5.8862e−17 0.199972 0.104156 122 164 99 15.171 QxN EeC 209.1 109.1 732.3 10.37689 2.7159e−25 0.285539 0.148994 203 230 88 39.951 LxxxN HhhhH 499.1 260.5 3907.2 15.30501 5.7912e−53 0.127739 0.066663 507 592 404 98.339 PxxxT HhhhH 231.4 120.8 1405 10.5292 5.2470e−26 0.164698 0.085959 243 272 184 40.088 DxxY ChhH 178 92.9 969.5 9.283777 1.3630e−20 0.1836 0.095833 206 235 171 43.716 FxxxE CchhH 122.3 63.9 1018.1 7.554523 3.4465e−14 0.120126 0.062721 143 163 111 22.37 RxxE ChhH 293.5 153.3 1085.3 12.21994 2.0770e−34 0.270432 0.141246 316 371 249 40.946 NxxxxR ChhhhH 126.6 66.1 967 7.704717 1.0776e−14 0.13092 0.068383 152 165 143 38.002 YxxxK HhhhC 127.5 66.6 735.6 7.820257 4.3817e−15 0.173328 0.090574 160 167 125 22.017 AxxQA HhhHH 113.8 59.5 1177.6 7.223678 4.1184e−13 0.096637 0.05053 135 130 105 15.993 IxxxN HhhhC 91.3 47.7 775.8 6.507313 6.2714e−11 0.117685 0.06154 111 118 95 9.688 RxxRE HhhHH 141.4 74 828.4 8.217981 1.7164e−16 0.17069 0.089275 148 167 139 40.58 DxxRA HhhHH 112.5 58.9 823.5 7.256832 3.2587e−13 0.136612 0.071469 136 140 120 23.245 DxxxxK CchhhH 102.7 53.7 685.9 6.958082 2.8484e−12 0.14973 0.07834 118 122 92 22.493 SxF CcE 155.7 81.5 1168.6 8.522011 1.2853e−17 0.133236 0.06974 164 189 98 30.377 ALxxE HHhhH 108.9 57 1224.1 7.032913 1.6407e−12 0.088963 0.046595 126 136 118 18.344 RxxxG HhhhC 350.8 183.7 1570 13.1164 2.2241e−39 0.223439 0.117029 383 456 329 66.416 FxxxD HhhhH 141.6 74.2 112.1 8.097839 4.5744e−16 0.126316 0.066187 163 181 136 33.51 GxxxxD CcchhH 262.4 137.5 2156 11.00743 2.8665e−28 0.121707 0.063779 313 341 244 68.196 FxxxK HhhhH 433.1 227.1 3125.6 14.19814 7.6861e−46 0.138565 0.072648 461 528 372 80.455 LAxxE HHhhH 111.2 58.3 1261.6 7.088647 1.0966e−12 0.088142 0.046234 119 134 110 18.25 WxxG EecC 110 57.7 703.5 7.185905 5.5069e−13 0.156361 0.08202 120 135 76 29.586 IxxxE CchhH 184.4 96.7 1441.8 9.229114 2.2271e−20 0.127896 0.067089 214 223 179 41.502 QExxR HHhhH 86.7 45.5 537.5 6.388227 1.3886e−10 0.161302 0.084616 105 117 90 16.26 TxxQ ChhH 610.7 320.4 2537.9 17.34901 1.6872e−67 0.240632 0.126252 622 765 470 110.722 DxxxF HhhhH 233.4 122.5 2397.6 10.28331 6.7728e−25 0.097347 0.051102 250 276 206 65.429 YxxS HhhC 95.6 50.2 655.1 6.67078 2.0931e−11 0.145932 0.076611 124 131 108 13.441 KxLG HhHC 102.4 53.8 672.1 6.913764 3.8864e−12 0.152358 0.080006 128 144 109 14.959 VxxxY HhhhH 206.8 108.6 3163.8 9.585411 7.3801e−22 0.065364 0.034334 215 230 166 46.981 SxxxxA CcchhH 87.1 45.8 977 6.259146 3.1360e−10 0.08915 0.046839 109 107 75 14.869 DxxxS HhhhC 148.4 78.1 662.7 8.474971 1.9691e−17 0.223932 0.117802 169 195 145 20.945 PxxxS HhhhH 340.3 179 1892.8 12.66679 7.4452e−37 0.179787 0.094585 368 431 290 56.359 YxxQ HhhH 398.5 209.7 2527.7 13.61767 2.5739e−42 0.157653 0.082949 422 461 320 108.519 GxxxxA CcchhH 152 80 1799.4 8.235044 1.4447e−16 0.084473 0.044459 171 183 138 54.309 GxH ChH 80.3 42.3 515.6 6.100545 8.7049e−10 0.155741 0.08202 82 102 62 19.027 QxxxI HhhhH 314.8 165.8 3351.4 11.86534 1.4406e−32 0.093931 0.049481 329 374 277 59.351 QxY EeE 187.6 98.9 1255.4 9.293234 1.2227e−20 0.149434 0.078777 177 235 142 33.071 ExxxxY HhhhhC 83.5 44 817.7 6.116442 7.7550e−10 0.102116 0.053839 103 108 77 31.322 NxxG HhhC 203.8 107.5 867.4 9.925044 2.7114e−23 0.234955 0.123919 222 254 190 28.398 PxxxQ ChhhH 94.4 49.8 653.3 6.577013 3.9291e−11 0.144497 0.076218 110 121 87 19.008 NW CE 87.6 46.2 354.5 6.527002 5.6617e−11 0.247109 0.13038 87 105 56 24.622 AxxAE HhhHH 133.4 70.4 1311.8 7.716222 9.6679e−15 0.101692 0.053677 154 159 139 22.18 QxxxA HhhhH 1147.9 606.8 7180.5 22.96015  9.5018e−117 0.159864 0.084501 1109 1333 879 166.872 DGS CCE 91.7 48.5 385.8 6.638838 2.6538e−11 0.237688 0.125656 99 91 19 9.104 TxEQ ChHH 131 69.3 722.9 7.799428 5.1196e−15 0.181215 0.095827 142 171 121 24.155 RExxA HHhhH 122.1 64.6 824.6 7.452817 7.4518e−14 0.148072 0.078335 134 164 119 28.012 TxxxxR ChhhhH 192.4 101.8 1444.8 9.314664 9.9140e−21 0.133167 0.070455 210 243 189 43.815 TxQ ChH 358.8 189.9 1213.7 13.34734 1.0422e−40 0.295625 0.156445 359 457 278 57.568 QxxL ChhH 83.7 44.3 539.5 6.175187 5.4110e−10 0.155144 0.082143 90 104 69 20.665 AxxxS HhhhH 815.9 432 6889.2 19.07625 3.1981e−81 0.118432 0.062711 858 1020 704 150.248 YxY EeE 228.8 121.2 2218 10.05802 6.7978e−24 0.103156 0.054624 222 239 163 85.831 NxxxM HhhhH 115 60.9 1093.3 7.131459 8.0001e−13 0.105186 0.055715 129 146 91 26.339 NxxS ChhH 191.8 101.6 1052.4 9.413467 3.9388e−21 0.18225 0.096549 203 237 171 61.026 PxxxQ HhhhH 489.4 259.6 2215.5 15.18275 3.8046e−52 0.220898 0.117159 516 612 413 65.861 RxxxxN HhhccC 89 47.2 591.1 6.340961 1.8630e−10 0.150567 0.079865 100 105 80 18.617 SxxxS HhhhH 612.2 324.9 3868.8 16.65308 2.3318e−62 0.15824 0.083981 621 709 477 120.508 DxxxM HhhhH 189.7 100.7 1555.5 9.171445 3.7589e−20 0.121954 0.064735 193 219 148 37.831 RExxxR HHhhhH 94.3 50.1 805.4 6.456703 8.6412e−11 0.117085 0.062155 107 122 98 21.898 MxxxV HhhhH 130.6 69.3 2641.7 7.453862 7.1767e−14 0.049438 0.026251 142 155 120 25.737 NxN ChH 250.9 133.3 909.1 11.0311 2.2760e−28 0.275987 0.146586 260 292 201 58.012 NxY CcE 207.7 110.3 1062.5 9.790792 1.0127e−22 0.195482 0.10385 211 222 130 39.035 TxW EeE 104.2 55.4 881.7 6.776643 9.9170e−12 0.118181 0.06281 107 120 84 28.988 QxxxE HhhhH 1661.6 884.6 7199.7 27.89439  2.5759e−171 0.230787 0.122866 1626 2046 1307 271.084 NxxxD HhhhH 469.1 249.9 2191.3 14.73567 3.1263e−49 0.214074 0.114022 479 561 383 103.469 ExxRA HhhHH 216.7 115.4 1491.6 9.81248 8.0321e−23 0.14528 0.07739 245 277 198 38.212 QxxG HhhC 411.9 219.5 1555.2 14.00967 1.1350e−44 0.264853 0.14116 472 534 404 65.505 PExxA HHhhH 127.9 68.2 958.9 7.506229 4.9065e−14 0.133382 0.071091 146 162 127 23.389 AAxxA HHhhH 198.7 105.9 3428 9.15901 4.1321e−20 0.057964 0.030896 229 253 204 29.278 LSxE CChH 112.6 60.1 832.4 7.032831 1.6319e−12 0.135272 0.072187 126 140 103 22.548 NxxT ChhH 183.6 98 984.6 9.105281 7.0144e−20 0.186472 0.099581 196 239 160 39.061 LAxxR HHhhH 94.9 50.7 1122.2 6.347006 1.7464e−10 0.084566 0.045204 115 122 104 19.449 PxxR HhhC 151.1 80.8 751.3 8.279371 1.0134e−16 0.201118 0.107541 175 195 150 34.249 RxxxY HhhhH 339.3 181.4 2495.4 12.17131 3.5410e−34 0.13597 0.072706 345 403 290 74.106 NxxxS HhhhC 99.5 53.2 474.7 6.7313 1.3826e−11 0.209606 0.112126 132 146 111 12.42 ERG HCC 94.3 50.4 359.7 6.658952 2.3048e−11 0.262163 0.140245 109 112 86 12.28 TxxxN HhhhH 500.1 267.6 2640.6 14.99574 6.3579e−51 0.189389 0.101328 526 619 420 87.708 ExxxN HhhhH 1238.3 662.5 5424.4 23.87465  4.6110e−126 0.228283 0.122138 1208 1512 928 223.973 SxxG HhhC 347.9 186.1 1537.7 12.6462 9.6469e−37 0.226247 0.121053 386 448 311 61.527 QxxxP HhhhH 83.8 44.8 376.3 6.199086 4.6927e−10 0.222695 0.119162 80 94 72 14.007 QxxR HhhH 1231.2 658.8 5042.5 23.91538  1.7473e−126 0.244165 0.130659 1202 1503 918 252.525 HxxxV HhhhH 215.1 115.2 2170.1 9.570428 8.4493e−22 0.09912 0.053066 227 314 174 79.055 PxxxD HhhhH 353.7 189.5 1593.3 12.70558 4.5110e−37 0.221992 0.118948 379 452 300 59.694 DxA ChH 999.6 535.7 3592.5 21.7314  8.6234e−105 0.278246 0.149103 966 1249 763 132.834 PxxxH HhhhH 126 67.5 704.1 7.482894 5.9047e−14 0.178952 0.095911 124 135 94 21.949 GFS CCC 100.2 53.7 618 6.636855 2.5936e−11 0.162136 0.086923 112 126 86 27.305 ExxH HhhH 621.9 333.5 3030.1 16.73683 5.7488e−63 0.205241 0.110077 623 720 476 164.84 VxxxR HhhhH 729.3 391.2 5584 17.72605 2.1028e−70 0.130605 0.070058 775 877 628 153.549 NH CE 115.1 61.8 505.6 7.245883 3.5376e−13 0.22765 0.122134 110 125 71 57.137 ExxxS HhhhH 1260.4 676.4 5947.2 23.85331  7.6202e−126 0.211932 0.113731 1205 1521 959 217.551 SxS ChH 515.9 277 2080.1 15.41924 1.0009e−53 0.248017 0.133156 515 629 395 104.302 GxxxH HhhhH 97.2 52.2 842.6 6.433257 9.9704e−11 0.115357 0.061937 105 128 93 24.109 QxxxM HhhhC 128.4 69 622.1 7.588773 2.6375e−14 0.206398 0.11087 145 165 124 21.509 RxxxxE CcchhH 143.1 76.9 1123 7.824477 4.0696e−15 0.127427 0.068462 170 180 127 25.24 AxP HcH 82.6 44.4 318.3 6.184656 5.1804e−10 0.259504 0.139426 89 108 80 13.458 SxxE ChhH 1232.3 662.1 5215.8 23.71508  2.0648e−124 0.236263 0.126945 1246 1512 984 208.985 WxD EeE 90.7 48.7 612.9 6.265784 2.9867e−10 0.147985 0.079514 90 101 68 39.123 ExxxA HhhhC 332.6 178.8 1550.9 12.22687 1.8204e−34 0.214456 0.115297 412 451 342 47.966 AxxxD HhhhH 831.5 447.2 4633.8 19.12119 1.3547e−81 0.179442 0.0965 825 1000 633 138.75 LxxxE HhhhH 1373.3 739.2 9254.6 24.31423  1.1055e−130 0.148391 0.079873 1341 1609 1068 245.576 FxxxT HhhhH 146.5 78.9 2060.1 7.767194 6.3018e−15 0.071113 0.038279 151 172 132 56.842 SxxxS HhhhC 130.9 70.5 730.4 7.568994 3.0401e−14 0.179217 0.096515 167 178 136 22.746 KxxxxS HhhccC 110.1 59.3 783.2 6.858237 5.5792e−12 0.140577 0.075739 133 143 120 23.932 KKxG HHcC 84.7 45.7 401.4 6.137295 6.8615e−10 0.211011 0.11375 101 108 85 7.445 YxG EcC 388.8 209.7 2305.9 12.97474 1.3641e−38 0.168611 0.090928 444 471 282 104.142 NxR ChH 288.4 155.7 1067.1 11.50362 1.0444e−30 0.270265 0.145939 299 351 241 95.177 TxxR ChhH 169.2 91.4 764.8 8.674858 3.3736e−18 0.221234 0.119488 181 197 129 46.634 QxxxD HhhhC 139.6 75.5 622.3 7.877462 2.7252e−15 0.224329 0.121252 167 191 146 19.277 PxxxV HhhhH 137.8 74.5 1643.4 7.506602 4.7630e−14 0.083851 0.04533 135 150 113 41.962 SxxxN HhhhC 129.1 69.8 738.4 7.458508 7.0377e−14 0.174837 0.094534 143 167 126 24.018 LxxE ChhH 118.3 64 675.1 7.137447 7.6498e−13 0.175233 0.094773 129 151 120 23.095 SxxxA HhhhH 836.8 452.6 7696.8 18.61578 1.8805e−77 0.108721 0.058802 847 1011 693 157.111 VxxxD HhhhH 249.5 135 1847.5 10.23183 1.1317e−24 0.135047 0.073088 272 319 238 36.088 TxR HcC 155.6 84.2 603.3 8.385416 4.1571e−17 0.257915 0.139598 166 212 128 41.373 SxxxI HhhhH 210.2 113.8 3246.1 9.197422 2.8543e−20 0.064755 0.035062 229 263 191 55.294 QxI EeE 286.5 155.2 2264.8 10.92249 7.1076e−28 0.126501 0.068519 289 334 222 58.719 RxxxI HhhhH 534.3 289.5 4313.7 14.89561 2.7733e−50 0.123861 0.067113 575 665 450 135.719 TKV EEE 147.9 80.2 815.1 7.963248 1.3456e−15 0.18145 0.098379 163 77 26 17.155 PxxQ HhhC 103.2 56 409.4 6.796772 8.7895e−12 0.252076 0.136685 118 126 92 20.413 DxR ChH 544.4 295.2 1961.9 15.73644 7.0040e−56 0.277486 0.150465 554 668 460 83.291 ExxRE HhhHH 240.2 130.3 1378.1 10.11552 3.7685e−24 0.174298 0.094564 265 290 224 43.827 KxxxxE HhhhcC 89.5 48.6 591.1 6.130528 6.9930e−10 0.151413 0.082166 111 120 96 19.403 RxxxD CchhH 159.2 86.4 800.2 8.292371 8.9467e−17 0.19895 0.107974 163 189 130 22.888 RxxxV HhhhH 506 274.6 3969.3 14.47043 1.4670e−47 0.127478 0.069191 534 589 412 103.446 ExxxF HhhhH 498.5 270.6 4158.3 14.32931 1.1281e−46 0.119881 0.065072 514 578 426 102.392 GxW CcE 181.9 98.7 1119.5 8.764418 1.4965e−18 0.162483 0.088199 181 213 154 55.342 QF HC 113.5 61.6 439.7 7.122281 8.7171e−13 0.258131 0.140203 123 141 96 23.442 MxxxD CchhH 103.9 56.5 674.3 6.595457 3.3788e−11 0.154086 0.083733 111 126 92 15.303 QxxxS HhhhC 134.1 72.9 655.1 7.607364 2.2573e−14 0.204702 0.111245 169 191 145 18.473 SxN ChH 239 129.9 996.5 10.26369 8.3511e−25 0.239839 0.130365 248 300 185 39.767 ExxxI HhhhH 758.2 412.4 6102.5 17.63348 1.0697e−69 0.124244 0.067581 799 923 676 129.885 LxxxR HhhhC 145 78.9 1150.8 7.709134 9.9857e−15 0.125999 0.068569 167 189 154 41.153 PxxxA HhhhH 816.8 444.6 6116.7 18.33146 3.6493e−75 0.133536 0.072684 847 1009 697 134.217 ExxxH HhhhH 551.1 300 2737.5 15.36047 2.4145e−53 0.201315 0.109602 593 676 485 111.491 NxxR HhhH 887.4 483.2 3933.1 19.63215 6.6235e−86 0.225624 0.12286 878 1025 668 165.101 DxxR HhhC 164.8 89.8 640.4 8.54263 1.0720e−17 0.257339 0.140153 182 212 152 29.523 LxxxQ HhhhC 114.8 62.5 916.8 6.847902 5.9099e−12 0.125218 0.068204 154 153 122 16.295 AxxRE HhhHH 138.9 75.7 940.9 7.575524 2.8327e−14 0.147625 0.080452 161 186 144 21.306 NxQ ChH 274.2 149.6 988.7 11.05835 1.6363e−28 0.277334 0.151307 286 338 234 51.75 NxxF ChhH 101.1 55.2 919.8 6.376146 1.4250e−10 0.109915 0.05999 117 125 105 16.826 MxxxE HhhhH 326.7 178.4 2165.2 11.59541 3.4291e−31 0.150887 0.082375 335 380 287 62.542 RxxxW HhhhH 132.1 72.2 1089.8 7.303532 2.2005e−13 0.121215 0.066206 140 142 113 23.636 DxxR HhhH 1950.8 1065.5 7576.4 29.25448  3.1941e−188 0.257484 0.140641 1854 2324 1449 369.877 RxxD HhhC 173.2 94.6 764 8.632735 4.8346e−18 0.226702 0.123828 178 201 123 28.849 NxxN HhhH 471.7 257.7 2067.4 14.2519 3.5119e−46 0.228161 0.12463 465 568 381 98.052 TxxxD HhhhH 397.4 217.1 1987.2 12.96478 1.5476e−38 0.19998 0.109253 415 496 340 67.131 LxxxA CchhH 132.5 72.4 1419 7.243531 3.4043e−13 0.093376 0.051052 155 175 146 29.062 ExxLA HhhHH 172.9 94.5 1763.6 8.285516 9.1556e−17 0.098038 0.053601 196 212 171 23.309 WxG EcC 102.7 56.2 603 6.522579 5.5005e−11 0.170315 0.093124 109 126 91 36.57 QxxxR HhhcC 88.9 48.6 430.5 6.128779 7.1237e−10 0.206504 0.112991 106 124 86 12.945 EQxxA HHhhH 117.1 64.1 862.2 6.87733 4.7983e−12 0.135815 0.074365 136 154 116 23.779 RxxxK HhhhC 144.3 79 584.7 7.89474 2.3580e−15 0.246793 0.135166 181 217 161 27.224 MxxxQ HhhhH 185.4 101.6 1387.6 8.640563 4.3854e−18 0.133612 0.073196 197 225 159 33.442 SxxxxN ChhhhH 104.2 57.1 951.4 6.431759 9.8602e−11 0.109523 0.060001 125 133 106 18.869 QxxN HhhC 139 76.2 567.1 7.738658 8.1377e−15 0.245107 0.134302 152 182 130 12.68 NxxA ChhH 312.9 171.5 1945.5 11.30439 9.8336e−30 0.160833 0.088165 329 396 273 78.395 SxxxV HhhhH 229.5 125.8 3159.2 9.431813 3.1065e−21 0.072645 0.039829 236 264 188 73.259 ExW EeE 134.4 73.7 812.2 7.414472 9.6618e−14 0.165476 0.090745 145 157 92 29.744 AxxxN HhhhH 512.5 281.1 3692.5 14.35617 7.6211e−47 0.138795 0.076137 534 649 438 86.064 RxxxM HhhhC 140.5 77.1 622.6 7.716933 9.5838e−15 0.225667 0.123805 164 183 130 24.647 YPE CCC 91.8 50.4 488 6.162289 5.7200e−10 0.188115 0.103238 100 112 83 19.149 EExxS HHhhH 108.6 59.6 688.3 6.641035 2.4611e−11 0.15778 0.086591 112 127 82 21.926 TxxxM HhhhH 152.5 83.7 2133.3 7.669962 1.3266e−14 0.071485 0.039242 160 182 126 40.979 ExxxxR HhhhcC 110.3 60.6 819.7 6.641153 2.4426e−11 0.134561 0.073884 136 139 121 21.653 LxS CcH 171 93.9 1159.4 8.298469 8.2824e−17 0.14749 0.080997 188 204 133 31.574 RExxR HHhhH 155 85.2 968.1 7.921336 1.8513e−15 0.160107 0.087988 177 191 146 31.035 SxT ChH 257.9 141.7 1197.1 10.3912 2.1709e−25 0.215437 0.118404 266 323 223 60.37 AxxEA HhhHH 188.2 103.4 2180.2 8.538938 1.0460e−17 0.086322 0.047445 224 245 202 24.32 PxxV ChhH 184.4 101.4 1437.5 8.554163 9.2654e−18 0.128278 0.070517 189 215 148 33.065 ExR CeE 196.5 108 664.3 9.299003 1.1605e−20 0.2958 0.162652 192 229 142 63.117 GxxxS HhhhH 289.5 159.2 2551.2 10.66269 1.1802e−26 0.113476 0.06241 307 350 258 47.168 TxxE EhhH 206.1 113.4 865.3 9.344617 7.4132e−21 0.238183 0.131001 237 251 121 20.44 QxxxP HhhcC 133.5 73.4 676.1 7.423599 9.0723e−14 0.197456 0.108619 153 159 130 20.698 TGP CCC 102.8 56.6 563.3 6.483433 7.1185e−11 0.182496 0.100399 112 129 81 24.898 NxxE ChhH 661 364 2655.9 16.75865 3.9327e−63 0.24888 0.137048 683 804 530 104.308 SxxT ChhH 228.9 126.1 1458.1 9.579028 7.6814e−22 0.156985 0.086477 245 277 190 35.722 DxxxQ HhhhH 930.8 512.8 4144.6 19.71989 1.1598e−86 0.224581 0.123724 958 1133 786 146.545 RxxxxN HhhhhC 97.2 53.6 765.7 6.176601 5.1150e−10 0.126943 0.069993 121 129 105 29.151 ExxxL HhhhH 1724.7 952.4 13302.4 25.97313  7.7159e−149 0.129653 0.071595 1714 2036 1346 325.45 SxxxxQ ChhhhH 176.9 97.8 1537.4 8.267115 1.0620e−16 0.115064 0.063607 215 218 163 45.171 YxxxI HhhhH 181.2 100.2 3381.2 8.207699 1.7172e−16 0.05359 0.029649 209 227 176 42.552 SxR ChH 317.2 175.7 1335.1 11.46073 1.6564e−30 0.237585 0.131564 313 366 248 69.543 EExxR HHhhH 314.5 174.2 1989.2 11.12684 7.2386e−29 0.158104 0.08758 353 399 306 47.077 QxxY HhhH 320.8 177.7 2179.5 11.20057 3.1483e−29 0.14719 0.081535 333 398 264 75.096 KxxxF HhhhH 328.2 181.8 2569.5 11.25855 1.6248e−29 0.127729 0.070772 360 395 288 57.303 ExxAA HhhHH 179.9 99.7 1794.4 8.26671 1.0592e−16 0.100256 0.055555 224 250 194 27.795 SGY CCC 105.1 58.2 565.7 6.482485 7.1196e−11 0.185788 0.102958 112 115 69 28.239 AxxxA HhhhC 318.2 176.4 2577.6 11.06323 1.4602e−28 0.123448 0.06843 397 453 358 43.621 RxxxxK HhhccC 99.7 55.3 673.8 6.235508 3.5171e−10 0.147967 0.082043 118 133 101 21.553 AxxxA HhhhH 2239.1 1243.1 25522.9 28.96403  1.4239e−184 0.087729 0.048705 1979 2515 1570 377.986 DxxxN HhhhH 594.3 330.2 2767.7 15.48977 3.2073e−54 0.214727 0.119292 614 755 502 85.14 KxxxxD HhcccC 159.3 88.5 1094.7 7.848456 3.2713e−15 0.145519 0.080853 193 202 143 24.959 AxxLA HhhHH 115.6 64.3 3480.5 6.461798 7.8277e−11 0.033214 0.018467 137 144 127 20.514 QxxxL HhccC 108.8 60.5 724.2 6.486287 6.8524e−11 0.150235 0.083542 127 143 117 20.405 TxxG HhhC 243.8 135.6 1055.4 9.954431 1.9130e−23 0.231002 0.128472 279 356 223 35.359 PxxR HhhH 724.7 403.3 3049 17.17996 2.9726e−66 0.237684 0.132276 728 858 571 110.512 DAxxA HHhhH 128.3 71.5 1234 6.928395 3.2679e−12 0.103971 0.057905 153 166 139 15.792 TxxE ChhH 1201.2 669 5025.4 22.09925  2.5443e−108 0.239026 0.133125 1180 1477 841 166.071 HxxxK HhhhH 307.2 171.1 1546.2 11.03354 2.0648e−28 0.198681 0.110656 328 403 273 68.068 TxxxI HhhhH 254.2 141.6 4781.1 9.604289 5.7955e−22 0.053168 0.029619 269 294 224 58.776 ExxxH HhccC 125.6 70 603.3 7.072015 1.2049e−12 0.208188 0.115991 152 164 101 33.629 HxY EeE 116.4 64.9 1054 6.606772 3.0212e−11 0.110436 0.061534 129 152 99 42.479 SxxY ChhH 128.7 71.7 933.9 7.000372 1.9754e−12 0.137809 0.07681 138 159 100 31.063 SxH ChH 103.8 57.9 491.9 6.428179 1.0206e−10 0.211018 0.11764 112 118 84 36.881 HxxH HhhH 144.4 80.6 873.5 7.464091 6.5267e−14 0.165312 0.092235 152 172 131 40.043 TxxxA HhhhH 589.6 329 6537.3 14.74006 2.7084e−49 0.09019 0.050333 586 719 479 134.41 YQ EC 128.8 71.9 489.2 7.264749 2.9907e−13 0.263287 0.146984 131 153 90 23.614 KVD EEE 140.3 78.3 634.6 7.478628 5.9323e−14 0.221084 0.123433 152 79 15 14.974 DxxG HhhC 433.3 241.9 1739.4 13.26116 3.0841e−40 0.249109 0.139082 486 577 385 81.211 AxxG HhhC 719.2 401.9 3735.5 16.75324 4.1779e−63 0.192531 0.107594 792 947 645 132.901 RxxxD HhhhC 158.5 88.6 698.8 7.943242 1.5551e−15 0.226817 0.126824 189 210 165 39.63 DxS ChH 748.1 418.8 2698 17.51035 9.5251e−69 0.277279 0.15521 787 947 603 113.524 DxxxS HhhhH 723.1 404.9 3662.5 16.77093 3.1011e−63 0.197433 0.110539 766 890 604 85.339 RAxxA HHhhH 103.1 57.8 1074 6.131959 6.6253e−10 0.095996 0.053785 113 124 100 18.536 GLN CCC 129 72.3 760.8 7.013456 1.8054e−12 0.169558 0.095002 132 159 111 25.459 NxG ChH 179.9 101 926.1 8.318476 6.9400e−17 0.194255 0.109052 183 215 142 55.758 SxN HcC 189.6 106.4 732.9 8.717704 2.2519e−18 0.258698 0.145238 193 209 143 29.06 SxxN ChhH 188.3 105.7 1076.5 8.458003 2.1068e−17 0.174919 0.098204 217 249 167 42.44 HxxR HhhH 430.4 241.7 2107.3 12.90365 3.3433e−38 0.204242 0.114677 460 530 368 106.265 PxGP CcCC 106.8 60 744.8 6.307076 2.1915e−10 0.143394 0.080514 96 126 75 24.033 DxxS ChhH 389.9 219.1 1996.9 12.23393 1.5902e−34 0.195253 0.109696 439 515 367 50.824 PF EE 115.2 64.7 915.2 6.507713 5.8473e−11 0.125874 0.070726 123 150 98 38.148 DxxxN HhhhC 170.6 95.9 797.1 8.136831 3.1755e−16 0.214026 0.120277 192 216 157 29.035 DxxxxK ChhhhH 237 133.2 1783.5 9.344319 7.0694e−21 0.132885 0.07471 276 303 240 48.784 LxA CcH 231.9 130.5 1826.3 9.214022 2.3961e−20 0.126978 0.071445 258 280 204 51.249 AExxR HHhhH 179.1 100.8 1506.8 8.070792 5.3200e−16 0.118861 0.06691 205 232 179 43.419 ExF EeE 256.9 144.6 1850.1 9.723236 1.8348e−22 0.138857 0.078174 265 291 209 54.885 VxxxT HhhhH 299.7 168.8 3669.7 10.31987 4.3157e−25 0.081669 0.045987 328 393 253 77.133 MxxxK HhhhH 312.3 175.9 2060 10.75693 4.2120e−27 0.151602 0.085374 342 376 280 61.438 SxQ HcC 103.6 58.4 439.2 6.360122 1.5890e−10 0.235883 0.132871 118 139 102 20.556 KxxxR HhhhH 1011.6 569.9 4523.9 19.79197 2.7224e−87 0.223612 0.125972 1037 1244 835 185.843 GFT CCC 104.1 58.7 639.9 6.224044 3.7409e−10 0.162682 0.091679 116 119 70 12.583 LxxxM HhhhH 250.7 141.3 5646.8 9.315799 9.0317e−21 0.044397 0.02503 266 296 217 74.072 SxxxE HhhhH 986.8 556.7 5025.9 19.33109 2.2728e−83 0.196343 0.110765 1001 1185 801 180.213 FxxG HhhC 119.4 67.4 990.8 6.56576 3.9456e−11 0.120509 0.067998 131 155 116 29.313 AAxxE HHhhH 158.9 89.7 1585.3 7.528216 3.8940e−14 0.100233 0.056558 183 206 146 24.986 DxxxA HhhhC 164 92.6 833.8 7.873273 2.6801e−15 0.19669 0.111028 203 231 171 17.346 KxxxxE CcchhH 180.8 102.1 1300.8 8.119417 3.5770e−16 0.138991 0.078458 213 237 161 45.712 ExxxE HhhhH 2968.6 1676.2 12774.8 33.86629  1.6289e−251 0.232379 0.131213 2577 3429 1992 488.767 AxxxG HhhhC 447.2 252.6 5044.8 12.5614 2.5867e−36 0.088646 0.050074 538 589 468 105.023 GYS CCC 109.9 62.1 605.1 6.400729 1.1963e−10 0.181623 0.10265 125 136 79 36.053 VxxxH HhhhH 143.8 81.3 1671.8 7.107051 8.9332e−13 0.086015 0.048628 177 191 154 30.317 YxP EeC 128.5 72.7 1189.1 6.761517 1.0351e−11 0.108065 0.061101 133 144 99 24.258 FxxQ HhhH 302.1 170.8 2695.6 10.37972 2.3182e−25 0.112072 0.063367 323 362 272 94.274 DxQ ChH 411.3 232.6 1454.6 12.78192 1.6375e−37 0.282758 0.159919 430 503 326 66.463 PxxxxE CcchhH 149.8 84.8 1475.9 7.272421 2.6673e−13 0.101497 0.057448 174 190 151 32.295 NxxF HhhH 192.4 108.9 1955.4 8.229704 1.4145e−16 0.098394 0.055709 197 227 159 41.112 KxxxG HhhhC 339.7 192.3 1593.3 11.33192 7.0668e−30 0.213205 0.120714 385 430 297 56.247 TxxxS HhhhH 331.2 187.6 2557.8 10.89634 9.0941e−28 0.129486 0.073325 363 417 288 67.112 MxxxS HhhhH 123.1 69.7 1368.3 6.561394 4.0179e−11 0.089966 0.050958 127 144 112 21.828 SxT HcE 136.9 77.6 476 7.363809 1.4202e−13 0.287605 0.162952 152 89 10 15.595 DxxxE HhhhC 108.3 61.4 472.6 6.422578 1.0479e−10 0.229158 0.129851 127 143 99 30.155 KExG HHhC 110.3 62.5 581.6 6.398256 1.2154e−10 0.189649 0.107478 136 145 117 18.342 YPG CCC 106.2 60.2 731.8 6.187731 4.6651e−10 0.145122 0.08227 120 121 81 23.496 EF HC 151.8 86.1 660.5 7.589196 2.5096e−14 0.229826 0.13039 170 189 133 13.525 RxD ChH 290.3 164.7 1023 10.67984 9.9908e−27 0.283773 0.16104 284 353 222 49.531 NxxG EecC 130.7 74.2 683.8 6.949277 2.8332e−12 0.191138 0.10849 128 157 103 42.528 PxxR ChhH 169.9 96.5 683.6 8.064812 5.7408e−16 0.248537 0.141143 202 229 165 39.661 RxxG EecC 324 184.1 1428.3 11.04835 1.7317e−28 0.226843 0.128887 327 383 243 62.915 PxxxQ CchhH 123 69.9 1169 6.551141 4.3072e−11 0.105218 0.059789 136 153 116 28.429 PxxxxL CchhhH 111.9 63.6 2362.3 6.141216 6.0977e−10 0.047369 0.026919 141 151 118 21.802 NxxxA HhhhH 576.4 327.6 4736.9 14.24538 3.6065e−46 0.121683 0.069165 609 710 517 99.648 LxQ CcH 123 69.9 744.9 6.668314 1.9809e−11 0.165123 0.093867 133 149 110 24.111 SxxN HhhC 140 79.6 683.6 7.198864 4.6921e−13 0.204798 0.116473 160 180 127 20.347 ExxxN HhhhC 264.5 150.5 1213.4 9.931293 2.3526e−23 0.217983 0.124013 322 370 285 39.172 NxxD ChhH 392.2 223.3 1771.2 12.09121 9.0805e−34 0.221432 0.126069 395 486 316 65.36 PxH ChH 116.7 66.4 517 6.603483 3.1220e−11 0.225725 0.128528 119 140 88 23.335 HxxQ HhhH 282.1 160.6 1397.3 10.18639 1.7536e−24 0.201889 0.114965 289 349 237 51.295 RF HC 157.1 89.5 702 7.654627 1.5033e−14 0.223789 0.127447 178 211 155 21.792 SxxxE CchhH 215.2 122.7 1155.5 8.838949 7.3988e−19 0.18624 0.106146 251 288 203 31.997 GxxxR HhhhH 452.9 258.2 3346.3 12.61114 1.3818e−36 0.135344 0.077167 493 565 420 109.722 RxY EeE 321.4 183.3 2132.7 10.66632 1.1077e−26 0.150701 0.08596 342 399 275 84.119 SxE ChH 1700.4 969.9 6349.9 25.48157  2.4624e−143 0.267784 0.152747 1615 2108 1254 281.17 DxxF ChhH 139.7 79.7 1183.9 6.957811 2.6034e−12 0.118 0.067327 157 188 138 23.423 RLxxE HHhhH 117.9 67.3 1249.5 6.341766 1.7026e−10 0.094358 0.053858 128 142 117 14.013 RxxR HhhC 223.6 127.7 881.5 9.180571 3.3400e−20 0.253659 0.144835 266 300 208 46.926 TxY EeE 525.3 300 3697 13.5691 4.6027e−42 0.142088 0.08115 562 610 309 124.673 DxxxD HhhhH 761.9 435.3 3587 16.6982 1.0362e−62 0.212406 0.121362 755 883 574 158.083 AxxxP HhhhH 152 86.9 915.3 7.34663 1.5470e−13 0.166066 0.094898 161 180 135 29.146 RxxxxG EeeecC 117.9 67.4 1073 6.357254 1.5436e−10 0.109879 0.062797 126 132 93 30.807 NxxxE HhhhH 854.2 488.3 4085.1 17.64964 7.8447e−70 0.209101 0.11952 856 1033 697 158.379 QxxxG HhhhH 228.4 130.7 1785 8.871047 5.4425e−19 0.127955 0.073249 248 274 196 42.146 PxS ChH 359.8 206 1492.8 11.54334 6.1661e−31 0.241024 0.137984 381 461 317 54.501 NxxR ChhH 186.9 1.07 849.5 8.259216 1.1290e−16 0.220012 0.125981 200 233 166 47.681 PxxK HhhC 134.8 77.3 516.7 7.0997 9.7499e−13 0.260886 0.149511 156 183 123 25.326 YxxE HhhH 584.6 335.1 3516.7 14.33068 1.0637e−46 0.166235 0.095283 614 727 494 119.936 SxEE ChHH 251.6 144.3 1525.5 9.392189 4.4475e−21 0.16493 0.094565 287 329 244 45.032 QY HC 142.8 81.9 492.7 7.372573 1.3154e−13 0.289832 0.16619 166 192 141 28.461 GxxA ChhH 294.2 168.8 2531.8 9.988638 1.2761e−23 0.116202 0.066679 325 356 261 83.468 YxR HcC 106.8 61.3 540.1 6.174179 5.0968e−10 0.197741 0.113477 114 128 81 23.631 RH HC 196.1 112.6 557.9 8.813158 9.7271e−19 0.351497 0.201757 209 257 138 31.879 RxE ChH 511.7 293.9 1726.9 13.94985 2.4681e−44 0.296311 0.170167 497 646 363 89.812 SxxQ HhhH 668.9 384.6 3261.9 15.4344 7.3145e−54 0.205065 0.117911 667 809 547 128.299 NxxxE CchhH 153.6 88.3 790.2 7.369784 1.3030e−13 0.194381 0.111774 156 207 126 35.628 RxxG HhhC 641.9 369.4 2583 15.31326 4.8017e−53 0.248509 0.143024 699 815 577 129.416 ERxxA HHhhH 126.2 72.6 932.1 6.543421 4.5159e−11 0.135393 0.077938 150 159 133 14.687 DxxD ChhH 374.5 215.7 1824.1 11.51857 8.0950e−31 0.205307 0.118228 400 447 317 54.562 RxE EeE 590.6 340.3 2432.2 14.6314 1.3602e−48 0.242825 0.13991 596 705 466 91.584 TxxxE HhhhH 774.7 446.4 4237.2 16.42699 9.2564e−61 0.182833 0.105356 784 932 643 131.967 FxF EeE 150.5 86.7 3210.8 6.941401 2.8496e−12 0.046873 0.027013 158 163 119 61.3 DxxxY HhhhH 276.7 159.5 2217.1 9.632198 4.3574e−22 0.124803 0.071944 302 341 247 76.638 KxxxL HhhhC 140.2 80.9 780.1 6.969798 2.4051e−12 0.179721 0.103656 176 196 150 17.239 TPG CCC 165 95.3 927.3 7.54283 3.4767e−14 0.177936 0.102732 177 222 121 37.415 GxxxD HhhhH 284.4 164.2 1944.5 9.799636 8.4522e−23 0.146259 0.084461 311 360 263 52.673 AxxEE HhhHH 123.6 71.4 897.5 6.441339 8.8743e−11 0.137716 0.079539 128 153 110 24.386 PxQ ChH 131.4 75.9 551.3 6.858192 5.3635e−12 0.238346 0.137697 138 175 114 22.393 RxxxP HhhcC 272.2 157.3 1341.2 9.751274 1.3823e−22 0.202953 0.117281 294 324 246 46.055 AxxxF HhhhH 315.3 182.3 6139.6 10.00393 1.0699e−23 0.051355 0.029686 326 365 264 134.406 SxxxG HhhhH 213.3 123.3 2125.3 8.349052 5.0903e−17 0.100362 0.058023 225 260 192 62.971 DxxQ ChhH 408.5 236.2 1714.9 12.0727 1.1263e−33 0.238206 0.137738 428 518 344 49.274 WxxS HhhH 124.5 72 1244.8 6.374403 1.3622e−10 0.100016 0.05784 141 157 99 38.938 GxxxQ HhhhH 268.1 155.1 2029.7 9.443637 2.6804e−21 0.132088 0.076405 287 315 235 38.085 RxxxR HhhcC 156.4 90.5 685.1 7.43411 8.0526e−14 0.228288 0.132114 188 216 156 31.425 RxxEA HhhHH 116.5 67.4 1018.4 6.184135 4.6459e−10 0.114395 0.066211 131 144 117 17.344 SxG HcC 511.7 296.4 2101.8 13.49625 1.2581e−41 0.243458 0.141004 562 662 462 69.467 GxxxQ ChhhH 116.1 67.2 821.3 6.217114 3.7900e−10 0.141361 0.08188 131 151 94 20.811 SxxL ChhH 205.4 119 1921 8.180858 2.0848e−16 0.106923 0.061934 227 253 190 40.531 HxxxS HhhhH 162.3 94 1134.4 7.35248 1.4535e−13 0.143071 0.082885 190 209 164 37.756 ExxxL HhhhC 161.1 93.4 989.5 7.354304 1.4394e−13 0.162809 0.094439 204 217 169 28.44 ExxxL HhhcC 201.6 117 1358 8.183729 2.0534e−16 0.148454 0.086144 245 275 222 28.455 YxP CcH 138.4 80.3 819.9 6.821998 6.7461e−12 0.168801 0.097974 164 177 116 35.479 VDK EEE 120.2 69.8 507.1 6.498036 6.2314e−11 0.237034 0.137624 136 56 15 13.141 SxxY HhhH 260.7 151.4 2441.4 9.174522 3.3449e−20 0.106783 0.062004 242 283 180 72.807 DxxY HhhH 368.3 213.9 2333.5 11.07501 1.2369e−28 0.157832 0.091673 388 427 293 84.209 LxV CcH 121.5 70.6 934.1 6.301937 2.1873e−10 0.130072 0.075572 137 149 116 30.831 PxY CeE 141.4 82.2 1016.8 6.814641 7.0386e−12 0.139064 0.080816 149 174 119 29.862 ExxxV HhhhH 640.3 372.2 5604 14.38506 4.7306e−47 0.114258 0.06641 656 754 552 112.908 GxG HcC 179.1 104.3 868.7 7.813594 4.2001e−15 0.20617 0.120016 192 224 167 44.519 DxxxG HhhhC 155.8 90.7 892.9 7.208474 4.2423e−13 0.174488 0.101604 181 201 138 20.459 SxG ChH 214 124.8 1455.8 8.356712 4.7893e−17 0.146998 0.085692 217 266 170 52.458 FxxxG EcccC 124.7 72.7 1449.8 6.254867 2.9197e−10 0.086012 0.050157 134 148 103 22.432 YxE EeC 112 65.3 580.6 6.12772 6.7195e−10 0.192904 0.112536 130 151 102 22.006 KxxxN HhhhH 655.3 382.3 3149.4 14.8929 2.7551e−50 0.208071 0.121401 667 805 560 144.066 NxxxxK ChhhhH 173.5 101.2 1409.7 7.454423 6.6649e−14 0.123076 0.071816 213 230 180 31.027 RxxxA HhhhH 1371.7 800.6 8918.1 21.15731 1.7498e−99 0.153811 0.089769 1345 1655 1122 268.179 QxxN HhhH 542.7 316.8 2555 13.56124 5.1153e−42 0.212407 0.123988 528 641 407 81.716 EExxA HHhhH 231.4 135.1 1569.7 8.663887 3.3802e−18 0.147417 0.086081 272 284 230 31.482 ExxxD HhhhH 1027.9 600.3 4905.2 18.63074 1.3593e−77 0.209553 0.122376 1027 1223 838 210.884 NxxQ HhhH 424.5 248 2082.1 11.94525 5.1603e−33 0.203881 0.11909 450 514 343 83.71 LxxxD HhhhH 439.7 256.8 3658.5 11.83281 1.9411e−32 0.120186 0.070204 493 552 428 61.228 AxxxT HhhhH 535.6 313 5359.1 12.96648 1.3850e−38 0.099942 0.058405 566 667 467 119.61 NxxxV HhhhH 198.5 116 2149.2 7.870098 2.5918e−15 0.09236 0.053993 214 241 168 42.296 AxG HcC 1022.2 597.7 4368 18.6919 4.3518e−78 0.23402 0.136825 1093 1343 884 165.19 SxxxD HhhhH 542.1 317.1 2830.2 13.40801 4.0538e−41 0.191541 0.112045 577 678 474 109.938 NxxS HhhC 143.9 84.2 634.7 6.988096 2.1104e−12 0.226721 0.132639 163 170 84 15.696 LxxxS HhhhH 425.1 248.9 5887 11.41524 2.5453e−30 0.07221 0.042274 453 514 374 80.723 DxxH ChhH 119.9 70.3 580.8 6.31013 2.0985e−10 0.206439 0.121037 148 156 136 27.653 GxxE ChhH 439 257.5 2293 12.00864 2.3858e−33 0.191452 0.112279 458 557 364 100.014 SxxR HhhH 897.4 526.5 4584.1 17.18044 2.7728e−66 0.195764 0.114856 903 1089 733 182.489 TxE ChH 1585.3 930.3 5513.1 23.55417  8.6926e−123 0.287551 0.168742 1546 2023 1133 224.257 RxxQ HhhC 134.4 78.9 541.4 6.75969 1.0508e−11 0.248245 0.145739 156 175 137 24.893 DxxG ChhH 206.7 121.6 1369.1 8.085262 4.5748e−16 0.150975 0.088814 241 271 193 44.741 NxG HhC 207.9 122.3 887 8.331963 5.9917e−17 0.234386 0.13792 233 274 207 47.58 ExxxP HhhhH 235.1 138.4 1108 8.792455 1.0954e−18 0.212184 0.124867 248 300 213 46.018 ExR HcC 208.6 122.8 704.9 8.523866 1.1834e−17 0.295929 0.174169 231 270 195 25.86 ExxxS HhhhC 285.9 168.3 1380.3 9.676894 2.8236e−22 0.207129 0.12191 348 362 277 39.886 TxxN ChhH 136.8 80.6 770.4 6.622398 2.6275e−11 0.17757 0.104563 153 183 121 29.388 RY HC 179.4 105.7 690.9 7.786927 5.2074e−15 0.259661 0.153012 192 229 157 45.361 PxD ChH 394.7 232.9 1487.4 11.54793 5.7222e−31 0.265362 0.156556 405 495 316 70.962 RxxR HhhH 1439.9 849.7 5869.7 21.89206  2.3219e−106 0.245311 0.144767 1337 1670 1062 351.183 PxxE ChhH 403.9 238.4 1641.8 11.59111 3.4386e−31 0.24601 0.145223 439 526 367 84.553 RxxxS HhhhC 140 82.7 696.5 6.718848 1.3667e−11 0.201005 0.118672 163 195 149 22.729 GxxN ChhH 131.3 77.5 799 6.424651 9.7711e−11 0.16433 0.097048 148 159 119 31.848 RxxxQ HhhcC 115 67.9 528.4 6.119902 7.0248e−10 0.217638 0.128534 143 161 101 18.483 TxxxT HhhhH 302.7 178.8 2535 9.61163 5.2002e−22 0.119408 0.07053 322 356 271 57.629 YxxS HhhH 346.5 204.8 2705.9 10.30319 4.9701e−25 0.128054 0.07567 407 448 323 85.864 ExxxA HhhhH 2448.2 1446.9 1497.3 27.6968  5.5984e−169 0.163508 0.096632 2360 2967 1770 391.906 NY HC 149.3 88.3 580 7.051042 1.3429e−12 0.257414 0.152234 152 175 108 37.209 LxxQ HhhH 1044.9 618.7 8365.8 17.80356 4.8141e−71 0.124901 0.07396 1054 1237 839 205.342 RxF EeE 260.1 154 2165 8.868217 5.4042e−19 0.120139 0.071144 273 304 219 68.858 GxxxT HhhhH 198.8 117.8 2285 7.668973 1.2522e−14 0.087002 0.051533 220 254 188 44.775 DxS CcH 196.1 116.2 853.5 7.979762 1.0971e−15 0.22976 0.136101 207 261 165 29.246 ExxxT HhhcC 171.6 101.7 869.5 7.378634 1.1868e−13 0.197355 0.116943 190 219 164 33.207 SxxxY HhhhH 187.1 110.9 2109.6 7.437346 7.4213e−14 0.08869 0.052556 221 241 180 52.01 RxxxT HhhhH 529 313.5 3140.6 12.82735 8.4563e−38 0.168439 0.099825 562 637 427 124.852 RxxxG EcccC 306.9 181.9 1622.6 9.832716 6.0107e−23 0.189141 0.112123 321 376 245 70.592 LxxxT HhhhH 391.1 231.9 5672.7 10.6763 9.4215e−27 0.068944 0.040877 411 468 353 70.436 DxxxT HhhhH 510.9 302.9 3002.8 12.59994 1.5506e−36 0.170141 0.100889 520 632 440 81.259 AxxxS HhhhC 167.8 99.5 1431 7.09616 9.3266e−13 0.117261 0.069543 206 230 172 23.643 TxN ChH 178.1 105.6 773 7.587086 2.4467e−14 0.230401 0.136666 187 207 125 44.663 DxxxH HhhhH 249.3 147.9 1441.7 8.798561 1.0190e−18 0.172921 0.102605 269 312 243 55.987 PxxxA CchhH 156.9 93.1 1242.7 6.870682 4.6541e−12 0.126257 0.074941 179 191 130 30.164 ExxQ ChhH 130.4 77.4 549 6.499866 6.0311e−11 0.237523 0.140984 148 174 121 22.094 DxR EeE 241.4 143.3 1105.4 8.782154 1.1928e−18 0.218382 0.129651 241 273 175 55.856 VxxxG HhhhC 156.3 92.9 1639 6.779043 8.7424e−12 0.095363 0.056653 194 215 174 26.154 AxxxE HhhhH 1813.4 1077.4 10751.7 23.6388  1.1253e−123 0.168662 0.100207 1799 2218 1404 311.318 DxxL ChhH 415.6 247 2867.7 11.22142 2.3305e−29 0.144925 0.086134 474 521 401 85.252 ExxxG HhhhC 343.9 204.4 1996.9 10.29927 5.2066e−25 0.172217 0.102356 401 457 326 66.121 SxxR ChhH 182.9 108.7 943.8 7.562349 2.9256e−14 0.193791 0.115201 190 221 174 40.459 YxxR HhhH 419.1 249.3 2896.8 11.25098 1.6663e−29 0.144677 0.086053 445 505 368 95.767 MxxxA HhhhH 219.1 130.3 4056.4 7.9041 1.9271e−15 0.054013 0.032129 233 243 178 49.827 KxxxQ HhhhH 1012.7 602.6 4794.5 17.86682 1.5795e−71 0.211221 0.125685 1071 1266 813 210.211 LxP CcH 462.1 275 3282.8 11.78653 3.3267e−32 0.140764 0.083772 517 589 393 66.229 NxQ CcE 241.5 143.8 921.8 8.867344 5.6237e−19 0.261987 0.156009 246 295 178 38.902 KxxxY HhhhH 398 237.1 2680.3 10.94733 4.9780e−28 0.148491 0.088449 422 490 362 82.687 AExxA HHhhH 177.1 105.6 2016 7.14469 6.4810e−13 0.087847 0.052392 206 232 184 27.754 QxP HcC 209.1 124.7 802.5 8.222219 1.4978e−16 0.260561 0.155407 224 278 195 37.428 SLP CCC 173.3 103.4 1051.9 7.242306 3.2273e−13 0.16475 0.098276 192 223 157 33.474 FxP CcH 163.8 97.7 1281.6 6.955237 2.5528e−12 0.127809 0.076247 187 207 154 26.16 PxxxE HhhhH 874.8 52.2 4147.7 16.51668 2.0506e−61 0.210912 0.12585 902 1091 727 146.13 DxF ChH 126.5 75.5 775.9 6.175381 4.8333e−10 0.163036 0.097325 138 154 118 25.97 DxR EcC 177.6 106.1 973.9 7.352718 1.4250e−13 0.18236 0.10895 180 199 138 42.006 YxxG EecC 245.6 146.8 1707.4 8.533428 1.0309e−17 0.143844 0.085957 256 293 188 44.484 ExxxQ HhhhC 184.1 110.1 858.5 7.555177 3.0917e−14 0.214444 0.128231 227 256 207 21.363 ExxR HhcC 256.7 153.6 992.7 9.051119 1.0566e−19 0.258588 0.154704 298 340 220 47.105 SxxD ChhH 740.5 443 3728.2 15.05505 2.3442e−51 0.198621 0.118834 773 907 609 152.565 RxxxS HhhhH 610.4 365.3 3531.9 13.54145 6.4805e−42 0.172825 0.103436 651 743 536 147.715 VPG CCC 166.4 99.6 1134.4 7.006024 1.7808e−12 0.146685 0.087813 192 224 166 28.485 KxxxE CchhH 374.5 224.2 1690.2 10.77748 3.2446e−27 0.221571 0.132651 395 458 302 76.148 CS HH 163.9 98.2 1268 6.908564 3.5402e−12 0.129259 0.077411 171 185 97 46.169 DxN ChH 418.4 250.6 1597.8 11.54559 5.7935e−31 0.26186 0.156827 433 521 349 57.653 AxxR HhhH 1961.9 1175.2 11570.1 24.20913  1.2946e−129 0.169566 0.101576 1808 2329 1411 364.394 FxxS HhhH 256.5 153.7 2817.2 8.532759 1.0219e−17 0.091048 0.054542 286 316 239 65.283 QxxG HhcC 372.1 222.9 1610.9 10.76288 3.8093e−27 0.230989 0.138391 426 493 371 65.685 HxxE HhhH 473.2 283.5 2266.1 12.04328 1.5453e−33 0.208817 0.125115 484 591 400 98.106 ExxG HhhC 927.7 556.2 3737.1 17.07683 1.6364e−65 0.248241 0.148819 1016 1234 849 159.494 TxxxH HhhhH 158.4 95 1225.2 6.777905 8.8108e−12 0.129285 0.077507 185 197 158 38.052 LxxxD CchhH 251 150.5 3175.1 8.394641 3.3309e−17 0.079053 0.047397 284 311 232 49.522 AxxxH HhhhH 353 211.8 3069.1 10.05093 6.5266e−24 0.115017 0.069026 373 426 305 99.698 DxxxV HhhhH 310.1 186.2 3011.7 9.379048 4.7618e−21 0.102965 0.06181 318 357 260 55.713 KxxxH HhhhH 282.8 169.8 1521 9.202981 2.5409e−20 0.18593 0.111622 301 362 241 94.486 SxxxQ ChhhH 160.3 96.2 1237.6 6.799777 7.5620e−12 0.129525 0.077763 181 204 150 36.116 QxxxA HhhhC 135.6 81.5 743.3 6.355858 1.5158e−10 0.18243 0.109602 174 199 154 22.04 KxxxD HhhhH 1559.9 937.5 7193.2 21.79635  1.8415e−105 0.216858 0.130335 1513 2010 1131 232.776 QxxI HhhH 566.2 340.5 4971.5 12.67152 6.0800e−37 0.113889 0.068494 599 676 469 89.516 ExxxxP HhcccC 160.6 96.6 1356.6 6.758251 1.0039e−11 0.118384 0.071199 205 218 173 30.38 YxS EeE 207.4 124.8 2356 7.603442 2.0554e−14 0.088031 0.052952 226 241 161 57.467 RxxEE HhhHH 141 84.8 971.6 6.385644 1.2352e−10 0.145121 0.087296 162 180 143 26.819 KxxxE HhhhC 340.5 204.9 1480.5 10.20524 1.3831e−24 0.22999 0.138401 402 482 329 38.586 DxxH HhhH 278.9 167.8 1432.4 9.123795 5.2948e−20 0.194708 0.117174 316 366 268 57.292 PxxN HhhH 169.2 101.9 934.3 7.064647 1.1733e−12 0.181098 0.109055 180 215 142 19.912 DxxR ChhH 424.4 255.7 1831.5 11.37574 4.0622e−30 0.231723 0.1396 442 539 373 86.94 ExxxT HhhhH 863.4 520.4 5003.9 15.88451 5.8664e−57 0.172545 0.103999 893 1035 747 128.695 PxxQ HhhH 457.1 275.6 2183.2 11.69472 9.9071e−32 0.209372 0.126244 485 582 395 66.605 RxR CcE 174.4 105.2 662.2 7.360225 1.3652e−13 0.263365 0.158821 171 202 137 45.897 AxxxM HhhhH 216.2 130.4 4230.4 7.627727 1.6849e−14 0.051106 0.030833 247 277 216 51.702 TxR ChH 214.3 129.3 922.7 8.061588 5.5443e−16 0.232253 0.140129 214 260 170 46.253 KxxxN HhhhC 184.1 111.1 842.5 7.431858 7.8583e−14 0.218516 0.131881 221 255 175 34.005 NxG EcC 266.8 161.1 1531.2 8.80872 9.1688e−19 0.174242 0.105181 275 305 146 82.701 RxxD ChhH 233.9 141.2 1264 8.276139 9.2445e−17 0.185047 0.111716 254 322 222 38.672 KxxxM HhhhH 288.8 174.5 2042.3 9.05073 1.0196e−19 0.141409 0.085429 306 360 253 62.497 SxxxxL ChhhhH 176.2 106.5 2832.5 6.880847 4.2026e−12 0.062207 0.03761 209 220 186 45.913 ExxAR HhhHH 162.3 98.2 1479.8 6.699894 1.4889e−11 0.109677 0.066333 184 208 161 27.669 QxD ChH 147.6 89.4 587.1 6.689422 1.6561e−11 0.251405 0.152227 151 172 107 36.91 TxEE ChHH 243.4 147.4 1546.4 8.314461 6.6330e−17 0.157398 0.095312 283 303 226 41.814 TxxxL HhhhH 483.5 292.8 8858.3 11.33044 6.5072e−30 0.054582 0.033058 520 621 429 125.095 ExxxM HhhhH 403.4 244.3 3338.3 10.57111 2.8892e−26 0.12084 0.073189 443 500 359 67.95 MxxxL HhhhH 227.6 137.9 5514.6 7.738694 7.0433e−15 0.041272 0.025002 267 288 224 56.394 YxxD HhhH 309.6 187.6 1936.7 9.372461 5.0951e−21 0.15986 0.096867 326 376 282 53.375 KY HC 311.9 189.1 1051.9 9.856121 4.8051e−23 0.296511 0.179808 330 402 272 38.686 RxP HcC 272.6 165.4 1046.7 9.080465 7.9710e−20 0.260438 0.158052 304 346 264 43.163 GLP CCC 279.5 169.6 1833.1 8.854745 6.0139e−19 0.152474 0.092541 296 355 249 50.76 SxxxT HhhhH 386.1 234.4 2954.6 10.3294 3.6971e−25 0.130678 0.079323 398 462 317 75.756 TxS ChH 302.5 183.7 1336.5 9.440319 2.7128e−21 0.226337 0.13743 310 375 236 52.207 NxE ChH 840.2 510.2 3189.6 15.94033 2.4469e−57 0.263419 0.159957 852 1054 677 130.26 DxxE ChhH 635.3 386.1 2788.7 13.66215 1.2445e−42 0.227812 0.138458 672 790 548 102.326 QxxxV HhhhH 290.2 176.4 3024.7 8.829936 7.4024e−19 0.095943 0.058319 316 371 260 85.71 GxV CcH 142.7 86.8 982.2 6.289195 2.2883e−10 0.145286 0.088337 147 166 125 31.929 PxA ChH 300.2 182.7 1377.9 9.335371 7.3154e−21 0.217868 0.132582 316 363 256 49.987 RxxQ HhhH 1120.7 683.5 5021.1 17.99374 1.5808e−72 0.223198 0.13612 1094 1312 857 202.148 NxS ChH 286.4 174.8 1258.8 9.10101 6.5075e−20 0.227518 0.138825 303 357 250 54.56 LPP CCC 180.4 110.2 1229.1 7.014972 1.6415e−12 0.146774 0.08962 178 217 156 21.42 RxN EeC 190.4 116.3 798.3 7.437105 7.5124e−14 0.238507 0.145653 179 217 124 38.991 IxxxK HhhhH 702.9 429.8 5778.4 13.69065 8.1501e−43 0.121643 0.074385 777 874 600 134.385 QxxH HhhH 240 146.8 1371.3 8.139332 2.8477e−16 0.175016 0.107058 250 298 214 48.318 RxQ EeE 235.1 143.8 1065.2 8.180894 2.0416e−16 0.22071 0.135042 232 277 172 39.053 DxxxE HhhhH 1501.2 918.8 7072.8 20.59983 1.9838e−94 0.21225 0.129901 1488 1867 1173 279.838 NxxxG HhhhH 155 94.9 1305.1 6.409783 1.0322e−10 0.118765 0.072698 175 191 155 33.083 PxxG HhhC 153 93.7 807.5 6.509851 5.4137e−11 0.189474 0.11609 174 190 141 20.911 DxxxA HhhhH 1305.7 800.2 8841.7 18.73718 1.7447e−78 0.147675 0.090505 1347 1647 1120 211.68 LY HC 138.9 85.1 796.1 6.165963 5.0248e−10 0.174476 0.106941 152 170 121 14.864 PxxL ChhH 222.4 136.4 2084.4 7.621642 1.7634e−14 0.106697 0.065419 243 272 201 46.144 VxxxF HhhhH 171.5 105.2 4285.6 6.549046 4.0245e−11 0.040018 0.02454 169 218 145 84.989 DxS CcE 237.4 145.6 1171.4 8.130164 3.0858e−16 0.202663 0.124293 257 272 120 29.903 ExxLE HhhHH 164.2 100.8 1515.9 6.539672 4.3457e−11 0.108318 0.066476 182 196 160 35.833 NxxP HhcC 135.6 83.2 655 6.145038 5.7748e−10 0.207023 0.127058 159 177 133 25.879 QxG HcC 492.4 302.3 1853.5 11.95146 4.6538e−33 0.26566 0.163098 546 659 433 83.868 AxxxL HhccC 142.7 87.6 1446 6.06968 9.0182e−10 0.098686 0.060602 188 204 166 29.997 TxP HcC 196.8 121 877.5 7.425272 8.1367e−14 0.224274 0.137858 217 250 174 33.337 ALP CCC 144.5 88.8 974.8 6.194927 4.1448e−10 0.148236 0.091132 150 179 129 30.435 YxxG HhcC 182 111.9 1042.3 7.012416 1.6727e−12 0.174614 0.10737 183 215 149 52.14 DxxT ChhH 458.9 282.2 2519.2 11.16131 4.4957e−29 0.182161 0.112025 479 585 405 89.773 YxF CcC 231.3 142.3 1699 7.788873 4.7756e−15 0.136139 0.083784 249 268 173 83.115 SxxA ChhH 337.5 207.7 2881.5 9.347949 6.2762e−21 0.117126 0.072087 377 424 299 84.421 FxI EeE 196.6 121 5105.9 6.953154 2.4724e−12 0.038504 0.023702 213 219 156 66.504 DxxN ChhH 214.4 132 1123.3 7.633453 1.6354e−14 0.190866 0.117519 239 297 184 64.208 DxxA ChhH 593.4 365.5 3282 12.64821 8.1426e−37 0.180804 0.111354 630 744 513 75.148 LxL CcH 176.2 108.5 1561.1 6.732965 1.1688e−11 0.112869 0.069526 189 207 155 35.143 IxxxY HhhhH 164.9 101.6 3264 6.374812 1.2709e−10 0.050521 0.03114 176 198 154 46.701 KxxG HhhC 867.2 534.5 3433.8 15.65894 2.0892e−55 0.252548 0.155669 924 1110 716 134.251 FxS EeE 172.8 106.5 2333 6.571821 3.4634e−11 0.074068 0.045664 180 194 131 54.814 QH HC 145.4 89.7 424 6.630426 2.4996e−11 0.342925 0.211441 164 184 139 29.8 TxxxxE ChhhhH 224.8 138.7 1943.5 7.580991 2.4056e−14 0.115668 0.071391 268 281 217 37.067 AxxKA HhhHH 166.5 102.8 1820.9 6.469686 6.8625e−11 0.091438 0.056448 206 240 174 25.798 QxxQ HhhH 966 596.4 4465.5 16.25654 1.4369e−59 0.216325 0.133567 947 1146 759 157.719 PxxxxR HhhhhH 238.9 147.5 2305.1 7.777629 5.1670e−15 0.10364 0.063993 272 286 215 41.213 AxxxY HhhhH 328.5 202.9 5012.4 9.005726 1.4841e−19 0.065537 0.040471 339 400 304 88.415 GxxG HhhC 171.9 106.2 1065.7 6.724762 1.2479e−11 0.161302 0.099611 215 221 165 33.951 WxxR HhhH 186.9 115.5 1454.6 6.929554 2.9705e−12 0.128489 0.079374 197 238 151 72.73 YxP EcC 223.8 138.3 1582.3 7.610135 1.9299e−14 0.14144 0.087407 250 288 204 54.263 TxxxxK ChhhhH 195.3 120.8 1644.2 7.037027 1.3767e−12 0.118781 0.073495 229 240 181 47.354 SxL HhC 258 159.7 1828 8.14081 2.7616e−16 0.141138 0.087371 307 339 232 50.261 FxY CcC 197.6 122.3 1387.8 7.126119 7.2715e−13 0.142384 0.088151 205 232 151 68.212 PxA CcH 167.1 103.6 1215 6.528079 4.6873e−11 0.137531 0.085236 193 221 168 47.747 ExxY HhhH 594.3 368.6 4092.2 12.32158 4.8612e−35 0.145228 0.090082 630 705 509 120.715 EH HC 228.4 141.7 666.7 8.20849 1.6592e−16 0.342583 0.212529 233 279 202 42.365 HxE ChH 196.5 121.9 874.7 7.277859 2.4319e−13 0.224648 0.139413 202 236 160 30.705 SxV ChH 170.8 106 1130.6 6.610197 2.7051e−11 0.15107 0.093764 179 206 139 31.222 FG HC 520.5 323.3 2395.3 11.79391 2.9912e−32 0.217301 0.134962 589 673 478 92.261 PxE ChH 750.1 466 2940 14.34588 8.1316e−47 0.255136 0.158508 757 942 616 106.696 YN HC 175.1 108.8 647.7 6.965652 2.3708e−12 0.270341 0.168011 195 225 138 30.624 TxxG HhcC 231.4 144.2 1143.9 7.77065 5.5443e−15 0.20229 0.126037 253 305 199 42.592 PCD CCC 199.2 124.2 1125.9 7.138468 6.6622e−13 0.176925 0.110285 217 252 156 38.178 KxxxP HhhcC 278.6 173.7 1410.7 8.496381 1.3851e−17 0.197491 0.123154 307 370 236 49.368 SxG EeC 176.7 110.2 1436.4 6.59101 3.0464e−11 0.123016 0.076729 189 214 121 62.904 FxxE HhhH 477.3 297.7 4177.8 10.79934 2.4039e−27 0.114247 0.071263 503 577 429 90.405 PGA CCC 212.4 132.7 1275.2 7.304192 1.9593e−13 0.166562 0.104098 240 269 170 62.409 DxD ChH 676.9 423.4 2579 13.47793 1.5116e−41 0.262466 0.164158 678 857 564 112.944 AxP HcC 365.8 228.9 1699.7 9.723656 1.6933e−22 0.215214 0.134695 409 472 349 60.063 NxL HhC 178 111.4 1250.4 6.609312 2.6962e−11 0.142354 0.089105 216 254 182 29.912 NxT ChH 211 132.2 967 7.375862 1.1589e−13 0.218201 0.136714 220 273 175 54.286 RxxE HhhH 2176.8 1363.9 9113.5 23.87027  4.4302e−126 0.238854 0.149656 2059 2638 1645 369.823 PLP CCC 188.1 117.9 1190.8 6.8156 6.5703e−12 0.157961 0.098979 204 232 172 26.197 EAxxR HHhhH 158.7 99.5 1610.8 6.130762 6.0465e−10 0.098522 0.061753 167 191 161 19.566 KxxxxE HhhccC 156.1 97.9 1140.5 6.155009 5.2325e−10 0.13687 0.08582 191 208 161 16.66 SxxN HhhH 444.5 278.8 2709 10.47981 7.4674e−26 0.164083 0.102906 464 532 373 113.319 NxxA HhhH 615.2 385.8 4642 12.19475 2.2966e−34 0.132529 0.083118 635 762 475 113.773 RxL EeC 168.4 105.6 952.5 6.475264 6.6512e−11 0.176798 0.110913 191 218 147 40.276 NxG HcC 306.9 192.6 1423.3 8.859907 5.6640e−19 0.215626 0.135299 345 401 287 66.643 DxA EcC 185.1 116.1 1247 6.718472 1.2812e−11 0.148436 0.093142 190 220 143 27.415 GF CE 273.1 171.4 2043.3 8.118336 3.2802e−16 0.133656 0.083872 291 321 212 77.768 LxxxL HhhhH 997.1 625.8 27017.2 15.01725 3.8391e−51 0.036906 0.023163 982 1113 809 274.286 ExxxQ HhhcC 146.5 92 726.3 6.086124 8.1812e−10 0.201707 0.12661 180 200 153 18.605 FG EC 205.6 129.1 2232.1 6.938062 2.7367e−12 0.092111 0.057832 230 269 170 66.387 TxA EcC 184.9 116.2 1173.5 6.718406 1.2831e−11 0.157563 0.098991 207 238 151 28.363 SxxP HhcC 304.6 191.7 1389.7 8.784923 1.1050e−18 0.219184 0.137925 344 403 238 54.435 YxE EeE 316.8 199.4 2122.7 8.730258 1.7640e−18 0.149244 0.093957 332 360 245 78.824 DxT ChH 325.9 205.3 1490.9 9.064351 8.8406e−20 0.218593 0.1377 337 422 287 58.774 SxG HhC 349.5 220.3 1705.1 9.325761 7.7389e−21 0.204973 0.129216 423 481 340 54.017 TxL ChH 162.1 102.2 1235.2 6.186318 4.2666e−10 0.131234 0.082742 169 187 128 40.459 TxxR HhhH 765 482.3 4295 13.66071 1.2139e−42 0.178114 0.1123 802 918 592 168.53 VxxxK HhhhH 731.6 461.5 5991.9 13.08537 2.7448e−39 0.122098 0.077025 816 955 651 134.532 SxxxL HhhhH 397 250.5 6529.4 9.436829 2.6110e−21 0.060802 0.038369 451 505 397 101.928 YxY CcC 288.7 182.3 1760.3 8.320026 6.1115e−17 0.164006 0.10358 293 340 185 93.01 YxxxA HhhhH 236.1 149.1 3917.6 7.260707 2.6193e−13 0.060266 0.038068 270 300 229 57.862 QxxL HhhH 1100.1 695.9 9726.7 15.90009 4.3300e−57 0.113101 0.071549 1109 1293 900 204.094 SxxxxE ChhhhH 255.8 161.8 2369.5 7.653127 1.3452e−14 0.107955 0.068296 294 334 245 39.409 HxD ChH 172.1 108.9 762.7 6.538917 4.3732e−11 0.225646 0.142806 177 217 150 51.532 RxxN HhhC 163.9 103.7 766.6 6.352558 1.4905e−10 0.213801 0.135319 196 217 168 28.434 NxxxK HhhhH 677.6 429.3 3506.7 12.79517 1.2149e−37 0.19323 0.122417 705 832 558 129.092 AxxxG HhhhH 369.9 234.4 5304.5 9.049512 9.7444e−20 0.069733 0.044196 418 481 332 62.946 DxxI HhhH 616.4 390.7 5172.8 11.87378 1.1089e−32 0.119162 0.075536 671 756 543 110.773 NxD ChH 495.1 313.9 2040 11.12133 6.9636e−29 0.242696 0.153854 510 643 414 84.876 SxD ChH 668.8 424.4 2701 12.92494 2.2948e−38 0.247612 0.157111 682 847 535 117.318 SxxS ChhH 231.8 147.1 1773.6 7.288639 2.1527e−13 0.130695 0.082959 256 295 197 65.521 DxxxR ChhhH 322.4 204.7 1923.2 8.701026 2.2763e−18 0.167637 0.106447 347 378 250 52.532 QxxF HhhH 273.6 173.9 2934.2 7.798778 4.2571e−15 0.093245 0.059253 289 316 237 60.216 DxxxL HhhhH 575.4 366.1 6298.7 11.27182 1.2269e−29 0.091352 0.058122 643 702 516 117.811 FxxR HhhH 351 223.5 3213.2 8.837814 6.6518e−19 0.109237 0.06957 379 434 315 101.994 RxxA HhhC 210.3 134 1114.3 7.029478 1.4404e−12 0.188728 0.120238 264 288 217 41.829 RxxxK HhhhH 1047 667.3 5094.2 15.76929 3.5148e−56 0.205528 0.130986 1109 1350 881 229.876 HxxD HhhH 233.8 149 1324.2 7.369841 1.1824e−13 0.176559 0.112552 244 288 201 45.746 ExxxP HhhcC 195.4 124.6 1156.3 6.718992 1.2654e−11 0.168987 0.107727 227 263 200 41.813 KxxxE HhhhH 2766.8 1765.1 13152.5 25.62491  5.5898e−145 0.210363 0.1342 2615 3468 1999 431.109 TxxN HhhH 437.5 279.1 2805.4 9.989921 1.1590e−23 0.155949 0.099494 452 523 353 80.127 QxG HhC 389.7 248.6 1652.1 9.705388 2.0025e−22 0.235882 0.150503 468 545 384 68.89 TxD ChH 596.6 380.9 2366.4 12.06539 1.1295e−33 0.252113 0.160964 614 769 469 103.233 ExxG EecC 416.3 266 2056.9 9.876549 3.6490e−23 0.202392 0.129319 418 505 320 71.375 FxxxA HhhhH 223.3 142.7 5346.2 6.83435 5.5321e−12 0.041768 0.0267 248 306 218 78.557 LxxxF HhhhH 296.1 189.7 7589.4 7.81986 3.5385e−15 0.039015 0.025001 334 359 275 99.347 RxG HcC 600.4 385.3 2430.5 11.94617 4.7458e−33 0.247027 0.158526 649 770 565 99.981 DxL ChH 284.2 182.4 1624.1 8.001921 8.4214e−16 0.174989 0.112298 276 344 233 62.639 PGxP CCcC 176.6 113.4 1196.2 6.242508 2.9487e−10 0.147634 0.094769 184 218 139 29.145 DxG HcC 432.5 277.7 1780.1 10.11318 3.3685e−24 0.242964 0.15599 473 585 397 65.071 DxG HhC 361.9 232.4 1588.1 9.195611 2.5922e−20 0.227882 0.146327 420 495 336 60.8 RxxN HhhH 493 316.8 2440.1 10.61521 1.7471e−26 0.202041 0.129815 501 583 395 101.528 AxxQ HhhH 1213 780.1 7792 16.34001 3.4909e−60 0.155672 0.100112 1229 1452 953 204.164 ExxN HhhH 1108.5 713.4 5126.3 15.94207 2.2333e−57 0.216238 0.13917 1069 1307 840 232.803 DxV ChH 274.2 176.5 1472.4 7.839595 3.1082e−15 0.186227 0.119867 292 321 232 52.187 TxxxG EcccC 266.6 171.7 1990.3 7.577823 2.3879e−14 0.13395 0.086262 296 340 245 61.191 AxV CeE 213.1 137.3 2617.4 6.642462 2.0749e−11 0.081417 0.052467 243 276 193 40.286 ExxKR HhhHH 190.5 122.9 1294.5 6.413164 9.7168e−11 0.147161 0.094917 220 245 190 33.813 SxL ChH 229.3 147.9 1709.6 7.001759 1.7166e−12 0.134125 0.086519 245 278 192 47.142 DxP ChH 163.2 105.3 784.1 6.063957 9.1857e−10 0.208137 0.134297 175 196 132 27.338 AxG HhC 719.4 465.5 3596.3 12.61434 1.2059e−36 0.200039 0.12943 843 967 694 130.922 QxxA HhhH 1224.8 792.5 8547.3 16.12184 1.2114e−58 0.143297 0.092719 1219 1484 974 208.072 PxxxL HhhhH 274.8 178.1 3402.7 7.445908 6.4391e−14 0.080759 0.052333 312 341 258 76.433 GAD CCC 214.2 138.8 1524.5 6.711627 1.3044e−11 0.140505 0.091053 221 284 180 35.942 RxT EeC 1805 117.1 856 6.301282 2.0319e−10 0.210864 0.136844 190 211 127 41.096 IxQ EeE 206.3 134 2177 6.450579 7.4700e−11 0.094763 0.061539 224 231 178 52.446 PxxxK HhhhH 653.9 424.7 3404.9 11.88889 9.2174e−33 0.192047 0.124727 683 814 550 106.479 DGR CCC 235.9 153.2 1180.8 7.15978 5.5359e−13 0.19978 0.129763 266 295 185 31.236 YH HH 259.5 168.6 1432.6 7.45738 6.0182e−14 0.181139 0.117657 236 291 175 73.31 PxxL HhhH 608.9 395.6 6143.7 11.08991 9.3855e−29 0.09911 0.064384 643 716 482 107.923 RxxG HhcC 659.6 428.8 2824.2 12.10492 6.8433e−34 0.233553 0.151816 731 878 617 99.95 ExY EeE 264 171.7 2049.9 7.357882 1.2583e−13 0.128787 0.083765 278 310 235 72.719 DxxQ HhhH 723.6 471.1 3555.4 12.48768 5.9445e−36 0.203521 0.132515 770 883 627 128.257 LxxE HhhH 1464.3 953.5 12363.8 17.21774 1.3074e−66 0.118434 0.077123 1431 1679 1159 242.872 ExxG HhcC 744.6 484.9 3281.4 12.77534 1.5440e−37 0.226915 0.147772 841 980 713 126.74 ExxxE HhhhC 174.4 113.6 865.2 6.122948 6.2923e−10 0.201572 0.131275 217 256 201 29.344 VxP CcH 241 157.2 1873.4 6.980528 1.9763e−12 0.128643 0.083925 283 319 238 39.774 AS HC 387 252.5 1734.3 9.157518 3.6376e−20 0.223145 0.145589 431 493 330 68.227 TxxD ChhH 532.6 347.6 3154.7 10.52015 4.7150e−26 0.168827 0.11018 570 661 449 96.783 KxG HhC 794.3 518.5 3293.5 13.19624 6.3329e−40 0.241172 0.157426 873 1027 674 123.629 TxK ChH 363.6 237.5 1518.2 8.90932 3.5284e−19 0.239494 0.156432 358 438 263 46.819 YxR EeE 222.6 145.4 1667.1 6.697394 1.4262e−11 0.133525 0.087238 235 256 181 62.069 ExxxK HhhhH 3252.3 2124.9 15568.8 26.31791  8.1352e−153 0.208899 0.136488 2973 4024 2223 531.075 LxxxI HhhhH 431.1 282 13352.3 8.970538 1.9380e−19 0.032287 0.021123 457 511 375 146.35 CxA CcC 240 157.1 1719.3 6.936502 2.6998e−12 0.139592 0.091386 251 295 175 79.348 QxxV HhhH 486.1 318.5 4621.8 9.73421 1.4329e−22 0.105175 0.068907 514 576 420 74.196 NxxK ChhH 267.5 175.3 1255.7 7.503694 4.2292e−14 0.213029 0.139633 301 336 254 43.698 ExxL HhhC 231.1 151.5 1603.1 6.7972 7.1660e−12 0.144158 0.094498 281 317 238 41.927 PGT CCC 187.5 122.9 1179.6 6.152747 5.1368e−10 0.158952 0.104216 207 228 155 38.844 SxxxK HhhhH 834.7 547.3 4847.5 13.04413 4.6206e−39 0.172192 0.112901 874 1041 709 151.146 QxxS HhhH 573.5 376.2 3395 10.78583 2.7025e−27 0.168925 0.110817 610 690 489 100.464 RxG HhC 536.7 352.1 2365.3 10.66383 1.0247e−26 0.226906 0.148858 591 683 523 90.687 KH HC 254.7 167.1 760.9 7.669848 1.2101e−14 0.334735 0.219625 272 327 207 55.477 DxQ CcE 200.1 131.3 843.7 6.532723 4.4296e−11 0.23717 0.155639 228 251 167 22.113 ExxN HhhC 219.4 144 1018.4 6.778934 8.2548e−12 0.215436 0.141417 266 312 235 36.571 GP EE 210.9 138.4 1127.3 6.574937 3.2980e−11 0.187084 0.12281 208 255 159 43.308 ExH EeE 193.8 127.3 1158.7 6.249782 2.7732e−10 0.167256 0.109845 210 230 172 59.385 IxY EeE 243 159.7 3724.8 6.738568 1.0556e−11 0.065238 0.042872 281 307 206 68.244 TS CH 275.6 181.2 1047.3 7.71034 8.6337e−15 0.263153 0.173029 270 302 172 48.603 AA HC 564.4 371.6 2472.5 10.85223 1.3234e−27 0.228271 0.150281 617 755 525 87.719 HxxxA HhhhH 224.3 147.7 2542.3 6.491995 5.6070e−11 0.088227 0.058106 255 282 222 55.81 RxS EeC 232.6 153.2 1206.4 6.864615 4.5085e−12 0.192805 0.126997 243 291 130 99.543 AxP CcH 300.6 198.2 1840.7 7.701465 9.0209e−15 0.163307 0.107667 349 397 279 55.725 AxxP HhcC 384.9 253.9 1977.2 8.806219 8.7288e−19 0.194669 0.128413 430 503 365 64.191 AxxG HhcC 596.4 393.6 3729.4 10.81149 2.0296e−27 0.159918 0.105527 706 816 603 104.595 VxxxS HhhhH 240.9 159 3366.1 6.65677 1.8435e−11 0.071567 0.047228 286 320 238 57.927 GxF CcE 309.7 204.4 2645.7 7.664502 1.1912e−14 0.117058 0.07727 359 372 247 73.042 AxN HcC 206.2 136.2 1076.8 6.420579 9.1640e−11 0.191493 0.126461 233 274 193 36.263 QxxK HhhH 1225.8 809.9 5705.9 15.77567 3.0884e−56 0.21483 0.141944 1252 1543 971 183.382 SxY EeE 224.1 148.1 2359.2 6.447301 7.5251e−11 0.09499 0.06279 259 270 162 64.803 DxDG CcCC 197.6 130.7 1653 6.102896 6.9206e−10 0.11954 0.079041 179 191 98 30.41 AxxxE CchhH 196.6 130 1472.9 6.114589 6.4488e−10 0.133478 0.088278 231 266 193 34.905 KxxxL HhhhH 975 645.5 8499.3 13.48896 1.1986e−41 0.114715 0.075953 1031 1221 860 169.471 TxH EeE 235.2 155.8 1626.2 6.691361 1.4731e−11 0.144632 0.095796 262 288 193 60.839 YxxT HhhH 223.7 148.3 2165.8 6.417924 9.1255e−11 0.103287 0.068461 239 265 193 48.734 SA CH 566.6 375.7 2576.3 10.65475 1.1178e−26 0.219928 0.145839 552 686 411 118.754 DxxN HhhH 709.7 470.7 3574.6 11.82169 2.0234e−32 0.19854 0.13168 758 884 582 111.272 RxG EeC 261.5 173.5 1393.1 7.141804 6.1825e−13 0.187711 0.124531 263 313 216 70.077 ExxL HhhH 2067.7 1372.8 16331.3 19.59683 1.0853e−85 0.12661 0.084059 2024 2416 1566 366.474 DxT EeC 210.2 139.6 1345.2 6.313609 1.8180e−10 0.156259 0.103764 231 261 175 42.758 GVP CCC 226.5 150.5 1776.5 6.477441 6.1803e−11 0.127498 0.084706 271 290 172 35.726 NxxE HhhH 551.2 366.4 2767 10.36368 2.4310e−25 0.199205 0.132425 569 681 482 93.396 QxxP HhcC 214.3 142.7 978 6.490339 5.7784e−11 0.219121 0.145866 252 286 217 34.293 

1-39. (canceled)
 40. A method for increasing the number of high quality crystal packing motifs in a target protein of modifying a protein sequence to improve its crystallization properties for high-resolution X-ray crystallographic structure determination, comprising a. providing a sub-epitope library containing local crystal-packing motifs in the PDB that span at most two-successive regular secondary structural elements and flanking loops, wherein each sub-epitope is ranked by p-value according to its overrepresentation in crystal-packing interfaces formed by crystal structures in the PDB that do not have excessively close inter-protein contacts; b. identifying one or more specific candidate sites in the sequence of the target protein for introduction of each sub-epitope in the library by: i. using a computer program to search a protein sequence database for proteins homologous to the target protein; ii. using a computer program to perform a multiple sequence alignment of the target sequence with the homologous proteins identified by the search program; iii. using a computer program to predict the secondary structure of the target protein based on its sequence; and iv. specifying exact sites in the target protein for introduction of a sub-epitope from the library based on the occurrence of residues similar to those in the sub-epitope at aligned positions in one of the homologous protein sequences and on conservation of the secondary structure of the sub-epitope in the target protein; and c. prioritizing sub-epitopes for introduction via mutagenesis at the specific sites identified for that sub-epitope in the target protein based on the overrepresentation p-value of the sub-epitope in crystal-packing interfaces; and d. further prioritizing sub-epitopes for introduction via mutagenesis at the specific sites identified for that sub-epitope in the target protein based on whether the number of sub-epitopes of equal or better overrepresentation p-value is increased by the required mutations in the target sequence; and e. obtaining a mutant protein sequence of the target protein based on the sub-epitope prioritization steps, expressing this mutant protein sequence in an expression system, and purifying the expressed mutant protein.
 41. The method of claim 40, in which the sub-epitope library comprises the sequences in tables 1-38.
 42. The method of claim 41, in which the candidate sub-epitopes for substitution at the candidate sites is selected from tables 8 or
 12. 43. (canceled)
 44. The method of claim 40, in which a mutant protein sequence is m<:pressed in an ex:pression system, and the expressed mutant protein is crystallized and its structure is determined using high-resolution X-ray crystallography.
 45. A method for increasing the number of high quality crystal packing motifs in a target protein of modifying a protein sequence to improve its crystallization properties for high-resolution X-ray crystallographic structure determination, comprising a. providing a sub-epitope library containing local crystal-packing motifs in the PDB that span at most two-successive regular secondary structural elements and flanking loops, wherein each sub-epitope is ranked by p-value according to its overrepresentation in crystal-packing interfaces formed by crystal structures in the PDB that do not have excessively close inter-protein contacts; b. identifying one or more specific candidate sites in the sequence of the target protein for introduction of each sub-epitope in the library by: i. using a computer program to search a protein sequence database for proteins homologous to the target protein; ii. using a computer program to perform a multiple sequence alignment of the target sequence with the homologous proteins identified by the search program; iii. using a computer program to predict the secondary structure of the target protein based on its sequence; and iv. specifying exact sites in the target protein for introduction of a sub-epitope from the library based on the occurrence of residues similar to those in the sub-epitope at aligned positions in one of the homologous protein sequences and on conservation of the secondary structure of the sub-epitope in the target protein; and c. prioritizing sub-epitopes for introduction via mutagenesis at the specific sites identified for that sub-epitope in the target protein based on the overrepresentation p-value of the sub-epitope in crystal-packing interfaces; and d. further prioritizing sub-epitopes for introduction via mutagenesis at the specific sites identified for that sub-epitope in the target protein based on whether the number of sub-epitopes of equal or better overrepresentation p-value is increased by the required mutations in the target sequence; and e. obtaining a mutant protein sequence of the target protein based on the sub-epitope prioritization steps and wherein the mutant protein sequence is expressed in an expression system to provide a mutant protein with the mutant protein sequence, and wherein the expressed mutant protein is purified, crystallized, and its structure is determined using high-resolution X-ray crystallography.
 46. The method of claim 45, in which the sub-epitope library comprises the sequences in tables 1-38.
 47. The method of claim 46, in which the candidate sub-epitopes for substitution at the candidate sites is selected from tables 8 or
 12. 48. (canceled)
 49. A method of modifying a protein sequence to improve its crystallization-properties for high-resolution X-ray crystallographic structure determination, comprising a. providing a sub-epitope library comprising the sequences in tables 1-38 containing local crystal-packing motifs in the PDB that span at most two-successive regular secondary structural elements and flanking loops, wherein each sub-epitope is ranked by p-value according to its overrepresentation in crystal-packing interfaces formed by crystal structures in the PDB that do not have excessively close inter-protein contacts; b. identifying one or more specific candidate sites in the sequence of the target protein for introduction of each sub-epitope in the library by: i. using a computer program to search a protein sequence database for proteins homologous to the target protein; ii. using a computer program to perform a multiple sequence alignment of the target sequence with the homologous proteins identified by the search program; iii. using a computer program to predict the secondary structure of the target protein based on its sequence; and iv. specifying exact sites in the target protein for introduction of a sub-epitope from the library based on the occurrence of residues similar to those in the sub-epitope at aligned positions in one of the homologous protein sequences and on conservation of the secondary structure of the sub-epitope in the target protein; and c. prioritizing sub-epitopes for introduction via mutagenesis at the specific sites identified for that sub-epitope in the target protein based on the overrepresentation p-value of the sub-epitope in crystal-packing interfaces; and d. further prioritizing sub-epitopes for introduction via mutagenesis at the specific sites identified for that sub-epitope in the target protein based on whether the number of sub-epitopes of equal or better overrepresentation p-value is increased by the required mutations in the target sequence; and e. obtaining a mutant protein sequence of the target protein based on the sub-epitope prioritization steps and wherein the mutant protein sequence is expressed in an expression system to provide a mutant protein with the mutant protein sequence, and wherein the expressed mutant protein is crystallized and its structure is determined using high-resolution X-ray crystallography. 